☆ 4.7 Review

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

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ACTA PHARMACOLOGICA SINICA (2021)

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Article Biochemical Research Methods

Prognosis and personalized treatment prediction in TP53-mutant hepatocellular carcinoma: an in silico strategy towards precision oncology

Chen Yang et al.

Summary: This study retrospectively analyzed 1135 HCC patients and developed a random forest-based prediction model to estimate TP53 mutational status, as well as a robust poor prognosis-associated signature which showed superior ability to predict survival in TP53-mutant patients. In silico screening revealed three targets and two agents that might have potential therapeutic implications in high-PPS patients, presenting a comprehensive view of potential treatment strategy.

BRIEFINGS IN BIOINFORMATICS (2021)

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Review Cell Biology

Ferroptosis: machinery and regulation

Xin Chen et al.

Summary: Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death caused by lipid peroxidation. Lipoxygenase is the main promoter of ferroptosis, while GPX4 is the central repressor of this process.

AUTOPHAGY (2021)

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Article Biology

Exploring the Role of Endoplasmic Reticulum Stress in Hepatocellular Carcinoma through mining of the Human Protein Atlas

Natasa Pavlovic et al.

Summary: Hepatocellular carcinoma is typically diagnosed in late stages with scarce therapeutic options due to lack of predictive biomarkers. Experimental evidence suggests ER-stress is involved in liver cancer initiation and progression. 44 ER-stress-associated proteins were identified as prognostic markers in liver cancer.

BIOLOGY-BASEL (2021)

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Review Cell Biology

Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy

Pranavi Koppula et al.

Summary: The overexpression of SLC7A11 promotes tumor growth while causing significant metabolic reprogramming costs for cancer cells. Cancer cells with high expression of SLC7A11 exhibit glucose- and glutamine-dependency, presenting potential metabolic vulnerabilities for therapeutic targeting.

PROTEIN & CELL (2021)

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Article Oncology

3-Methyladenine-enhanced susceptibility to sorafenib in hepatocellular carcinoma cells by inhibiting autophagy

Fangfang Zhao et al.

Summary: The study demonstrates that the autophagy inhibitor 3-MA can alleviate acquired drug resistance of sorafenib by suppressing autophagy activity, enhancing sensitivity to advanced hepatocellular carcinoma therapy.

ANTI-CANCER DRUGS (2021)

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Article Medicine, Research & Experimental

LncRNA NBR2 inhibits tumorigenesis by regulating autophagy in hepatocellular carcinoma

Jia-Qi Sheng et al.

Summary: Long noncoding RNA NBR2 acts as a tumor suppressor gene in hepatocellular carcinoma, inhibiting cell proliferation, invasion, and migration, as well as promoting proliferation by repressing autophagy. The study provides a novel treatment strategy for hepatocellular carcinoma.

BIOMEDICINE & PHARMACOTHERAPY (2021)

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Review Cell Biology

Ferroptosis: molecular mechanisms and health implications

Daolin Tang et al.

Summary: Cell death can be executed through different subroutines, such as ferroptosis which is an iron-dependent form of non-apoptotic cell death. Ferroptosis can occur through two major pathways, driven by redox imbalance and abnormal expression of redox-active enzymes. The process is precisely regulated at multiple levels, with the transcription factor NFE2L2 playing a central role in anti-ferroptotic defense.

CELL RESEARCH (2021)

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Article Medicine, Research & Experimental

Endoplasmic reticulum stress: Multiple regulatory roles in hepatocellular carcinoma

Jiacheng Wu et al.

Summary: Endoplasmic reticulum (ER) stress plays a critical role in the occurrence and progression of hepatocellular carcinoma (HCC), driving tumorigenesis and progression of tumors. Targeting the ER stress signaling pathway and related molecules may have a key role in anti-HCC strategies.

BIOMEDICINE & PHARMACOTHERAPY (2021)

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Article Medicine, Research & Experimental

Inhibition of autophagy with Chloroquine enhanced apoptosis induced by 5-aminolevulinic acid-photodynamic therapy in secondary hyperparathyroidism primary cells and organoids

Liyun Zeng et al.

Summary: The study successfully conducted experiments on the effect of 5-aminolevulinic acid-mediated photodynamic therapy (5ALA-PDT) on SHPT primary cells and organoids, demonstrating its phototoxic effect on these cells and tissues. The research indicates that autophagy and apoptosis play crucial roles in its mechanism, with autophagy influencing cell survival and apoptosis inhibition. Therefore, the use of autophagy inhibitors can enhance the sensitivity of SHPT cells and organoids to 5-ALA-PDT treatment.

BIOMEDICINE & PHARMACOTHERAPY (2021)

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Review Biochemistry & Molecular Biology

Molecular mechanisms and physiological functions of mitophagy

Mashun Onishi et al.

Summary: Mitophagy is a fundamental cellular mechanism for degrading mitochondria, regulated by specific receptors or ubiquitin molecules. Its dysfunction is associated with various pathological conditions, highlighting its biological significance in maintaining cellular homeostasis.

EMBO JOURNAL (2021)

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Article Gastroenterology & Hepatology

Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan

Ryosuke Tateishi et al.

Summary: Although type 2 diabetes mellitus is a known risk factor for hepatocellular carcinoma, the incidence in diabetic patients is usually below efficient surveillance levels. This study aimed to identify risk factors for HCC in diabetic patients and found that the FIB-4 index is a valuable predictor for HCC development, helping to identify high-risk patients for surveillance.

JOURNAL OF GASTROENTEROLOGY (2021)

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Article Oncology

STOML2 potentiates metastasis of hepatocellular carcinoma by promoting PINK1-mediated mitophagy and regulates sensitivity to lenvatinib

Yahui Zheng et al.

Summary: The study revealed that overexpression of STOML2 in HCC is associated with metastasis, poor overall survival, and higher recurrence rates. Upregulation of STOML2 accelerates colony formation, migration, and invasion of HCC cells.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Article Medicine, Research & Experimental

YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis

Ruize Gao et al.

Summary: The study reveals the critical role of YAP/TAZ in suppressing ferroptosis and establishing Sorafenib resistance in hepatocellular carcinoma (HCC). This highlights YAP/TAZ-based rewiring strategies as potential approaches to overcome HCC therapy resistance. The findings provide new insights into improving the efficacy of current therapies in cancer treatment.

EMBO MOLECULAR MEDICINE (2021)

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Article Gastroenterology & Hepatology

The changing scenario of hepatocellular carcinoma in Italy: an update

Francesca Garuti et al.

Summary: In Italy, over the last 15 years, there has been a gradual increase in age of HCC patients, a rise in non-viral cases, and improvements in clinical management. Different treatment methods have shown positive outcomes, leading to an overall increase in survival rates.

LIVER INTERNATIONAL (2021)

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Article Pharmacology & Pharmacy

ACSL family: The regulatory mechanisms and therapeutic implications in cancer

Jing Quan et al.

Summary: The deregulation of fatty acid metabolism is associated with cancer development, with ACSL family members playing different roles in cancer progression, some promoting cancer and some having inhibitory effects, while also participating in cell death processes. ACSLs may serve as important therapeutic targets and biomarkers for cancer treatment.

EUROPEAN JOURNAL OF PHARMACOLOGY (2021)

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Article Cell Biology

A Marine Terpenoid, Heteronemin, Induces Both the Apoptosis and Ferroptosis of Hepatocellular Carcinoma Cells and Involves the ROS and MAPK Pathways

Wen-Tsan Chang et al.

Summary: Heteronemin, a marine natural product, has shown inhibitory effects on hepatocellular carcinoma cells by inducing apoptosis through modulation of ROS, MAPK signaling pathways, and other mechanisms. These findings suggest that with structural modification, heteronemin could potentially serve as a potent therapeutic agent against HCC.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2021)

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Article Biochemistry & Molecular Biology

Autophagy-Related Chemoprotection against Sorafenib in Human Hepatocarcinoma: Role of FOXO3 Upregulation and Modulation by Regorafenib

Flavia Fondevila et al.

Summary: Early acquisition of sorafenib resistance in advanced hepatocarcinoma is a critical factor for poor prognosis. Autophagy, particularly regulated by FOXO3, is involved in modulating chemosensitivity. Targeting FOXO3-mediated autophagy may significantly improve the clinical efficacy of sorafenib in HCC.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Medicine, General & Internal

Hepatocellular carcinoma

Josep M. Llovet et al.

Summary: Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global health challenge with rising incidence projected to exceed 1 million cases by 2025. Infection by hepatitis B and C viruses remains a major risk factor for HCC, while non-alcoholic steatohepatitis is emerging as a more common risk factor in Western countries. Advances in systemic therapies for HCC, including immunotherapies and targeted therapies, are expected to revolutionize the management of this disease.

NATURE REVIEWS DISEASE PRIMERS (2021)

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Review Cell Biology

Characteristics and Biomarkers of Ferroptosis

Xin Chen et al.

Summary: The induction and consequences of regulated cell death (RCD) result in changes in gene and protein expression, biochemical pathways, cell morphology, and size. Among different forms of RCD, ferroptosis, driven by iron overload and lipid peroxidation, is implicated in various pathological conditions and diseases. The ferroptotic response can be fine-tuned through oxidative stress and antioxidant pathways, and a series of inducers or inhibitors have been developed targeting metabolism-related proteins.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Article Biochemistry & Molecular Biology

GSK3B induces autophagy by phosphorylating ULK1

Hye Young Ryu et al.

Summary: ULK1, a critical enzyme in autophagy induction, is activated by GSK3B through phosphorylation of specific amino acids S405 and S415, promoting interaction with key autophagy proteins. High levels of phosphorylation at these sites were observed in pancreatic cancer cell lines with increased autophagy, suggesting a potential role in tumorigenesis.

EXPERIMENTAL AND MOLECULAR MEDICINE (2021)

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Review Biochemistry & Molecular Biology

The Role of IGF/IGF-1R Signaling in Hepatocellular Carcinomas: Stemness-Related Properties and Drug Resistance

Mai-Huong Thi Ngo et al.

Summary: This review summarizes the evidence of dysregulated IGF/IGF-1R signaling, especially in HBV-related HCC, and highlights the regulation of cancer stemness expression and drug resistance. Current clinical treatments and potential therapies targeting IGF/IGF-1R signaling for the treatment of HCC are discussed.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemistry & Molecular Biology

Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma

Juncheng Wei et al.

Summary: Hepatocellular carcinoma is a major cause of cancer mortality globally, and its pathogenesis involves the interplay of ER stress and unfolded protein response. The liver's susceptibility to ER stress, due to its functions in protein synthesis and detoxification, may play a crucial role in HCC development and treatment response.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cell Biology

Mitochondria-targeted antioxidant, mito-TEMPO mitigates initiation phase of N-Nitrosodiethylamine-induced hepatocarcinogenesis

Sachin Shetty et al.

Summary: Targeting mitochondrial oxidative stress at the early stages of hepatocarcinogenesis with mito-TEMPO showed promising results in preventing HCC. Mito-TEMPO pre-treatment protected mice from NDEA-induced damage by normalizing liver injury markers.

MITOCHONDRION (2021)

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Article Biochemistry & Molecular Biology

Quiescin sulfhydryl oxidase 1 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by driving EGFR endosomal trafficking and inhibiting NRF2 activation

Jialei Sun et al.

Summary: QSOX1 acts as a cellular prooxidant in HCC, sensitizing cells to oxidative stress by inhibiting NRF2. There is a negative correlation between QSOX1 and NRF2 expression in tumor tissues from HCC patients, and QSOX1 can enhance sorafenib-induced ferroptosis.

REDOX BIOLOGY (2021)

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Article Oncology

Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis

Alberto Zanetto et al.

Summary: The study reveals a significant association between altered platelet function and hepatocellular carcinoma in patients with cirrhosis, suggesting the potential benefit of inhibiting hyper-functional platelets. The differences in platelet function may have important clinical implications for treatment.

CANCERS (2021)

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Article Cell Biology

HBx induces hepatocellular carcinogenesis through ARRB1-mediated autophagy to drive the G1/S cycle

Yiming Lei et al.

Summary: The protein ARBB1 plays a critical role in HBV-related hepatocellular carcinoma by modulating autophagy and the CDKN1B-CDK2-CCNE1-E2F1 axis, suggesting it may be a potential therapeutic target for HCC.

AUTOPHAGY (2021)

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Article Oncology

ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway

Junru Chen et al.

Summary: Lipid metabolic reprogramming is crucial for hepatocellular carcinoma (HCC) development, with long chain acyl CoA synthetase 4 (ACSL4) playing a key role in modulating de novo lipogenesis and promoting HCC progression. Mechanistically, ACSL4 upregulates SREBP1 to regulate lipogenesis in HCC cells, with a positive correlation between ACSL4 and SREBP1 expression in HCC patients, suggesting a potential combinational biomarker for predicting HCC.

CANCER LETTERS (2021)

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Article Oncology

EPHB2 Activates β-Catenin to Enhance Cancer Stem Cell Properties and Drive Sorafenib Resistance in Hepatocellular Carcinoma

Hoi-Wing Leung et al.

Summary: This study identified a EPHB2/beta-catenin/TCF1 positive feedback loop that enhances cancer stemness and sorafenib resistance in HCC, providing a targetable axis to combat acquired drug resistance in HCC.

CANCER RESEARCH (2021)

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Review Immunology

Necroptosis, pyroptosis and apoptosis: an intricate game of cell death

Damien Bertheloot et al.

Summary: Cell death is a fundamental physiological process in all living organisms, playing important roles in embryonic development, organ maintenance, aging, immune responses, and autoimmunity. Recent research has significantly increased our understanding of the mechanisms orchestrating different types of programmed cell death and how they affect the balance of cell fates. Various modalities of cell death, such as apoptosis, necroptosis, and pyroptosis, have been studied to highlight both common and unique pathways and their impact on the surrounding cells and the organism as a whole.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Article Pharmacology & Pharmacy

Jujuboside B Inhibits the Proliferation of Breast Cancer Cell Lines by Inducing Apoptosis and Autophagy

Lin Guo et al.

Summary: JB induces apoptosis and autophagy in human breast cancer cell lines, mediated by NOXA and AMPK signaling pathway. In vivo study confirms JB's anti-breast cancer effect by suppressing tumor growth. Autophagy plays a pro-survival role in attenuating apoptosis induced by JB.

FRONTIERS IN PHARMACOLOGY (2021)

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Review Biochemistry & Molecular Biology

Metformin Actions on the Liver: Protection Mechanisms Emerging in Hepatocytes and Immune Cells against NASH-Related HCC

Yueqi Zhang et al.

Summary: Nonalcoholic fatty liver disease (NAFLD) is closely associated with the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and can progress to nonalcoholic steatohepatitis (NASH) leading to hepatocellular carcinoma (HCC). Metformin, a first-line drug for T2DM, may reduce risks for various cancers including HCC and protect against NASH-related HCC.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Gastroenterology & Hepatology

Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis

Roser Pinyol et al.

Summary: This study revealed higher rates of ACVR2A mutations (10%) in NASH-related hepatocellular carcinoma (HCC), along with a novel mutational signature that distinguishes NASH-HCC from HCCs of other etiologies.

JOURNAL OF HEPATOLOGY (2021)

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Article Cell Biology

Long Non-Coding RNA LINC01572 Promotes Hepatocellular Carcinoma Progression via Sponging miR-195-5p to Enhance PFKFB4-Mediated Glycolysis and PI3K/AKT Activation

Shihui Lai et al.

Summary: The study identified an lncRNA LINC01572 that was upregulated in T2DM-related HCC, contributing to HCC progression by promoting cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition. LINC01572 acts as a ceRNA of miR-195-5p to increase PFKFB4 levels, enhancing glycolysis and activating PI3K/AKT signaling pathway in HCC cells. This mechanism ultimately leads to the malignancy of HCC.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Biochemistry & Molecular Biology

Interplay of autophagy and cancer stem cells in hepatocellular carcinoma

Magdelyn Mei-Theng Wong et al.

Summary: Liver cancer is the sixth most common cancer and the fourth leading cause of cancer deaths worldwide. Autophagy plays a crucial role in the development and progression of hepatocellular carcinoma, as well as in the self-renewal and differentiation of liver cancer stem cells.

MOLECULAR BIOLOGY REPORTS (2021)

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Review Cell Biology

Ferroptosis in liver disease: new insights into disease mechanisms

Jing Wu et al.

Summary: This review outlines the characteristics of ferroptosis, its relevance in liver diseases, and the molecular mechanisms underlying common liver diseases. Challenges and promises for future investigations in ferroptosis regulation as a potential therapeutic target in clinical practice are also highlighted.

CELL DEATH DISCOVERY (2021)

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Article Biochemistry & Molecular Biology

Vaccinia-related kinase 2 blunts sorafenib's efficacy against hepatocellular carcinoma by disturbing the apoptosis-autophagy balance

Sisi Chen et al.

Summary: Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options, and sorafenib is currently the only FDA-approved first-line targeted drug for advanced HCC. However, studies have shown that the imbalance between apoptosis and autophagy plays a key role in chemoresistance, and VRK2 has been identified as a factor contributing to sorafenib resistance in HCC by disrupting this balance. Targeting VRK2 to modulate the balance between autophagy and apoptosis may offer a new strategy for overcoming sorafenib resistance in HCC.

ONCOGENE (2021)

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Article Oncology

Ferroptosis is involved in the progression of hepatocellular carcinoma through the circ0097009/miR-1261/SLC7A11 axis

Ning Lyu et al.

Summary: In this study, circRNA circ0097009 was found to be significantly upregulated in HCC tissues and cell lines, and it acted as a competing endogenous RNA to regulate the expression of SLC7A11 by sponging miR-1261 in HCC. Circ0097009 may serve as a diagnostic biomarker for HCC and a potential therapeutic target for HCC treatment.

ANNALS OF TRANSLATIONAL MEDICINE (2021)

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Review Biochemistry & Molecular Biology

Mechanism of interaction between autophagy and apoptosis in cancer

Shreya Das et al.

Summary: Autophagy and apoptosis play significant roles in cancer, but they may exhibit dual effects on cancer cell survival as the disease progresses. Interactions between a complex array of biomarkers are crucial in maintaining coordination between the two pathways, influencing the survival or death of malignant cells.

APOPTOSIS (2021)

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Review Oncology

Selective autophagy

Mohammad Omar Faruk et al.

Summary: Selective autophagy, which degrades specific targets in a selective manner, plays a crucial role in maintaining cellular homeostasis by regulating diverse cellular functions.

CANCER SCIENCE (2021)

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Review Biochemistry & Molecular Biology

Mechanisms of DNA Methylation in Virus-Host Interaction in Hepatitis B Infection: Pathogenesis and Oncogenetic Properties

Dake Zhang et al.

Summary: Hepatitis B virus (HBV) infection leads to hepatic carcinoma development through genetic and epigenetic changes in liver cells, mediated by DNA methylation. Studies have shown that DNA methylation plays a crucial role in viral replication, cancer-related gene silencing, and hepatocellular carcinoma development.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Cell Biology

Autophagy Regulation on Pyroptosis: Mechanism and Medical Implication in Sepsis

Ran Guo et al.

Summary: The article reviews the harmful effects of pyroptosis in sepsis and the regulatory role of autophagy in combating pyroptosis and inflammation, highlighting the potential therapeutic applications in sepsis.

MEDIATORS OF INFLAMMATION (2021)

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Review Biochemistry & Molecular Biology

Ferroptosis in the tumor microenvironment: perspectives for immunotherapy

Huanji Xu et al.

Summary: Targeting ferroptosis as a new approach for anticancer therapy shows potential as it induces lipid peroxidation in cancer cells. Understanding how immune cells in the tumor microenvironment respond to lethal lipid peroxides may uncover new possibilities for cancer immunotherapy. This study provides an overview of the metabolic processes involved in ferroptosis and explores its roles in cancer immunity, highlighting the potential for targeted therapy.

TRENDS IN MOLECULAR MEDICINE (2021)

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Article Cell Biology

Anti-miR-518d-5p overcomes liver tumor cell death resistance through mitochondrial activity

Pablo Fernandez-Tussy et al.

Summary: miR-518d-5p modulates sorafenib resistance in HCC through inhibition of c-Jun/PUMA-induced apoptosis, and circulating miR-518d-5p emerges as a potential biomarker for lack of response to sorafenib.

CELL DEATH & DISEASE (2021)

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Article Cell Biology

PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway

Zhiqiang Han et al.

Summary: PNO1 is overexpressed in hepatocellular carcinoma (HCC) and promotes autophagy while inhibiting apoptosis of HCC cells through the MAPK signaling pathway, thereby advancing the progression of HCC.

CELL DEATH & DISEASE (2021)

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Article Immunology

Construction of a Ferroptosis-Related Nine-lncRNA Signature for Predicting Prognosis and Immune Response in Hepatocellular Carcinoma

Zhijie Xu et al.

Summary: This study investigated the association between differentially expressed lncRNAs and ferroptosis-related genes in HCC, identifying a nine-lncRNA-based prognostic model. The model could be a promising personalized tool for prognosis and immune response prediction in HCC patients.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Cell Biology

The AMPK/p27Kip1 Pathway as a Novel Target to Promote Autophagy and Resilience in Aged Cells

Lauren K. McKay et al.

Summary: p27(Kip1) was previously thought to only act as a cyclin-dependent kinase inhibitor, but it is now recognized as a crucial mediator of various cellular processes, including autophagy, cytoskeletal dynamics, cell migration, and apoptosis. The subcellular location of p27(Kip1) plays a critical role in determining its function, with cytoplasmic p27(Kip1) promoting cellular resilience and nuclear p27(Kip1) inhibiting cell cycle progression. Regulation of p27(Kip1) cellular localization through phosphorylation by kinases like Akt and AMPK contributes to its role in aging and cell fate.

CELLS (2021)

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Review Cell Biology

Calcium Signaling Regulates Autophagy and Apoptosis

Pramod Sukumaran et al.

Summary: Calcium serves as a crucial second messenger in regulating various physiological functions, such as cell growth/development, cell survival, and programmed cell death processes. The homeostasis of cytosolic calcium levels, maintained through coordination of proteins/pumps/Ca2+ channels and Ca2+ storage in organelles, is essential for cellular functions. Store operated Ca2+ entry (SOCE) mechanism, activated by calcium depletion, influences functions in both excitable and non-excitable cells, with potential implications in neurodegenerative conditions.

CELLS (2021)

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Article Cell Biology

Changes in Wnt and TGF-β Signaling Mediate the Development of Regorafenib Resistance in Hepatocellular Carcinoma Cell Line HuH7

Mustafa Karabicici et al.

Summary: In this study, it was found that regorafenib treatment activated Wnt/beta-catenin signaling only in hepatoblast-like HCC cell lines and induced enrichment of markers associated with hepatic stem/progenitor cells. On the other hand, regorafenib resistant cells demonstrated diminished Wnt/beta-catenin signaling activity and enhanced TGF-beta signaling activity. The inhibition of TGF-beta pathway in combination with regorafenib administration might increase regorafenib-induced cell death in HCC tumors with aberrant activation in the Wnt/beta-catenin pathway.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Oncology

Molecular Targets of Ferroptosis in Hepatocellular Carcinoma

Hao Liao et al.

Summary: Ferroptosis is a unique form of regulated cell death caused by intracellular iron accumulation and lipid peroxidation. Research progress on ferroptosis in hepatocellular carcinoma may lead to the development of novel therapeutic targets and markers to improve patient prognosis.

JOURNAL OF HEPATOCELLULAR CARCINOMA (2021)

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Article Gastroenterology & Hepatology

More Pronounced Hypercoagulable State and Hypofibrinolysis in Patients With Cirrhosis With Versus Without HCC

Alberto Zanetto et al.

Summary: This study found that patients with cirrhosis with HCC exhibit significantly more prothrombotic hemostatic profile, contributing to their increased risk of portal vein thrombosis and cirrhosis progression. On the other hand, hypercoagulability in patients with decompensated cirrhosis is more likely a consequence of chronic liver disease rather than a driver for cirrhosis progression.

HEPATOLOGY COMMUNICATIONS (2021)

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Article Oncology

Chronic liver disease enables gut Enterococcus faecalis colonization to promote liver carcinogenesis

Noriho Iida et al.

Summary: The study revealed that Enterococcus faecalis is abundant in the microbiota of patients with hepatitis C virus-related chronic liver disease, promoting liver carcinogenesis via the TLR4-Myd88 signaling pathway.

NATURE CANCER (2021)

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Review Biochemistry & Molecular Biology

From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways

Yaqiu Wang et al.

Summary: Pyroptosis, apoptosis and necroptosis are well-defined programmed cell death pathways, with growing evidence showing extensive crosstalk among them. PANoptosis, regulated by the PANoptosome complex, combines features of pyroptosis, apoptosis, and/or necroptosis. This new concept is critically involved in various diseases and may inform the development of new therapeutics.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2021)

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Review Gastroenterology & Hepatology

Autophagy in liver diseases

Elias Kouroumalis et al.

Summary: Autophagy plays a crucial role in liver diseases, including injuries, infections, cancers, and genetic disorders. The level of autophagy can have a significant impact on the progression of liver diseases.

WORLD JOURNAL OF HEPATOLOGY (2021)

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Review Oncology

The Role of Tumor Associated Macrophages in Hepatocellular Carcinoma

Yu Huang et al.

Summary: Hepatocellular carcinoma (HCC) is a common cancer worldwide, with chronic inflammation and tumor-associated macrophages playing crucial roles in its development and progression. Understanding the mechanisms by which macrophages contribute to HCC pathogenesis could lead to novel immunotherapies targeting macrophages.

JOURNAL OF CANCER (2021)

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Review Oncology

Ferroptosis is a type of autophagy-dependent cell death

Borong Zhou et al.

SEMINARS IN CANCER BIOLOGY (2020)

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Review Cell Biology

Mitochondria as playmakers of apoptosis, autophagy and senescence

Marianna Abate et al.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2020)

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Review Cell Biology

yIntegrated stress response in hepatitis C promotes Nrf2-related chaperone-mediated autophagy: A novel mechanism for host-microbe survival and HCC development in liver cirrhosis

Srikanta Dash et al.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2020)

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Article Gastroenterology & Hepatology

miR-541 potentiates the response of human hepatocellular carcinoma to sorafenib treatment by inhibiting autophagy

Wen-Ping Xu et al.

GUT (2020)

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Review Cell Biology

Role of regulatory miRNAs of the PI3K/AKT/mTOR signaling in the pathogenesis of hepatocellular carcinoma

Farzad Rahmani et al.

JOURNAL OF CELLULAR PHYSIOLOGY (2020)

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Review Oncology

The role of cell signaling in the crosstalk between autophagy and apoptosis in the regulation of tumor cell survival in response to sorafenib and neratinib

Laurence A. Booth et al.

SEMINARS IN CANCER BIOLOGY (2020)

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Review Biochemistry & Molecular Biology

Activation of mTOR Signaling Pathway in Hepatocellular Carcinoma

Gustavo Ferrin et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Biochemistry & Molecular Biology

Molecular Mechanisms: Connections between Nonalcoholic Fatty Liver Disease, Steatohepatitis and Hepatocellular Carcinoma

Tatsuo Kanda et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Gastroenterology & Hepatology

Advances in molecular classification and precision oncology in hepatocellular carcinoma

Sandra Rebouissou et al.

JOURNAL OF HEPATOLOGY (2020)

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Review Cell Biology

Ferroptosis: past, present and future

Jie Li et al.

CELL DEATH & DISEASE (2020)

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Article Oncology

Death-associated protein kinase 1 suppresses hepatocellular carcinoma cell migration and invasion by upregulation of DEAD-box helicase 20

Yide Huang et al.

CANCER SCIENCE (2020)

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Article Oncology

Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway

Ruijie Sun et al.

CANCER MEDICINE (2020)

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Review Genetics & Heredity

The clinicopathological and prognostic significance of P27kip in hepatocellular carcinoma patients: A systemic review and meta-analysis

Yongxiang Luo et al.

GENE (2020)

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Review Biochemistry & Molecular Biology

Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

Sandra Buratta et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Biochemistry & Molecular Biology

Hepatitis C Virus and Hepatocellular Carcinoma: When the Host Loses Its Grip

Kaku Goto et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Cell Biology

Autophagy and endocytosis - interconnections and interdependencies

Asa B. Birgisdottir et al.

JOURNAL OF CELL SCIENCE (2020)

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Article Oncology

Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy

Fenfen Hong et al.

WORLD JOURNAL OF SURGICAL ONCOLOGY (2020)

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Article Cell Biology

TNFAIP8 regulates autophagy, cell steatosis, and promotes hepatocellular carcinoma cell proliferation

Suryakant Niture et al.

CELL DEATH & DISEASE (2020)

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Review Biochemistry & Molecular Biology

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

Zhilin Zou et al.

CELL AND BIOSCIENCE (2020)

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Article Oncology

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ATG14 facilitated lipophagy in cancer cells induce ER stress mediated mitoptosis through a ROS dependent pathway

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An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model

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Metallothionein-1G Facilitates Sorafenib Resistance Through Inhibition of Ferroptosis

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A micro-RNA expression signature for human NAFLD progression

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Unique features associated with hepatic oxidative DNA damage and DNA methylation in non-alcoholic fatty liver disease

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Regulation of ER stress-induced autophagy by GSK3β-TIP60-ULK1 pathway

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The ω-3 polyunsaturated fatty acids prevented colitis-associated carcinogenesis through blocking dissociation of β-catenin complex, inhibiting COX-2 through repressing NF-κB, and inducing 15-prostaglandin dehydrogenase

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PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of Alcoholic Liver Disease

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Death-associated protein kinase 2: Regulator of apoptosis, autophagy and inflammation

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Steroid Receptor Coactivator 1 Promotes Human Hepatocellular Carcinoma Progression by Enhancing Wnt/β-Catenin Signaling

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ASPP2 attenuates triglycerides to protect against hepatocyte injury by reducing autophagy in a cell and mouse model of non-alcoholic fatty liver disease

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Genetic Variation in the PNPLA3 Gene Is Associated with Alcoholic Liver Injury in Caucasians

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Adenovirus Membrane Penetration Activates the NLRP3 Inflammasome

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The Autophagy Protein Atg12 Associates with Antiapoptotic Bcl-2 Family Members to Promote Mitochondrial Apoptosis

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cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms

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Enhancement of Canonical Wnt/β-Catenin Signaling Activity by HCV Core Protein Promotes Cell Growth of Hepatocellular Carcinoma Cells

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Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL

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Unfolded protein response activation contributes to chemoresistance in hepatocellular carcinoma

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Down-regulation of Death-associated Protein Kinase-2 Is Required for β-Catenin-induced Anoikis Resistance of Malignant Epithelial Cells

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Nonstructural 5A protein activates β-catenin signaling cascades: Implication of hepatitis C virus-induced liver pathogenesis

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Cytoplasmic functions of the tumour suppressor p53

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FLIP-mediated autophagy regulation in cell death control

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Hepatitis B virus X protein upregulates expression of SMYD3 and C-MYC in HepG2 cells

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Malarial Hemozoin Is a Nalp3 Inflammasome Activating Danger Signal

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Hepatitis C Virus Core Protein Augments Androgen Receptor-Mediated Signaling

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Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization

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Cell death and autophagy: Cytokines, drugs, and nutritional factors

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Immunohistochemical expression of components of the Akt-mTORC1 pathway is associated with hepatocellular carcinoma in patients with chronic liver disease

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Autophagosome formation: Core machinery and adaptations

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Toll-like receptors 1 and 6 are involved in TLR2-mediated macrophage activation by hepatitis C virus core and NS3 proteins

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Cytoplasmic mutant p53 increases Bcl-2 expression in estrogen receptor-positive breast cancer cells

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Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival

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The energy sensing LKB1-AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis

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NATURE CELL BIOLOGY (2007)

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Mitochondrial membrane permeabilization in cell death

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Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis

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NATURE CELL BIOLOGY (2006)

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Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells

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FEBS LETTERS (2006)

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DRAM, a p53-induced modulator of autophagy, is critical for apoptosis

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Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis

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CANCER CELL (2006)

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Hepatitis C virus core protein inhibits tumor necrosis factor alpha-mediated apoptosis by a protective effect involving cellular FLICE inhibitory protein

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JOURNAL OF VIROLOGY (2006)

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Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers

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INTERNATIONAL JOURNAL OF CANCER (2006)

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Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population

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INTERNATIONAL JOURNAL OF CANCER (2006)

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The association between diabetes and hepatocellular carcinoma: A systematic review of epidemiologic evidence

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CLINICAL GASTROENTEROLOGY AND HEPATOLOGY (2006)

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Functional specificity of the mammalian Beclin-Vps34 Pl 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking

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NATURE REVIEWS CANCER (2006)

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GENES & DEVELOPMENT (2006)

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Viral FLIP enhances Wnt signaling downstream of stabilized β-catenin, leading to control of cell growth

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Relation of endotoxin, endotoxin binding proteins and macrophages to severe alcoholic liver injury and multiple organ failure

H Fukui

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Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy

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CELL (2005)

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Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C-elegans

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CURRENT BIOLOGY (2005)

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Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA

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IKKβ couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis

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The coordinate regulation of the p53 and rnTOR pathways in cells

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

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Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study

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GUT (2005)

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Pro- and anti-apoptotic roles of c-Jun N-terminal kinase (JNK) in ethanol and acetaldehyde exposed rat hepatocytes

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EUROPEAN JOURNAL OF PHARMACOLOGY (2005)

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Hepatitis B virus X protein (HBx)-induced apoptosis in HuH-7 cells: Influence of HBV genotype and basal core promoter mutations

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SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY (2004)

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The hepatitis C virus NS5A protein activates a phosphoinositide 3-kinase-dependent survival signaling cascade

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Stabilized β-catenin promotes hepatocyte proliferation and inhibits TNFα-induced apoptosis

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JM Adams

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The absence of up-regulation of telomerase activity during regeneration after partial hepatectomy in hepatitis B virus X gene transgenic mice

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Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma

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Pro-apoptotic function of HBV X protein is mediated by interaction with c-FLIP and enhancement of death-inducing signal

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EMBO JOURNAL (2003)

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Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress

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AMERICAN JOURNAL OF PATHOLOGY (2003)

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β-Catenin expression in hepatocellular carcinoma:: A possible participation of β-catenin in the dedifferentiation process

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JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY (2002)

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Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase

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TGF-beta induces apoptosis through Smad-mediated expression of DAP-kinase

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FLICE-inhibitory proteins: Regulators of death receptor-mediated apoptosis

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Hepatitis B virus X protein: a multifunctional viral regulator

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Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis

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Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner

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DAP kinase activates a p19(ARF)/p53-mediated apoptotic checkpoint to suppress oncogenic transformation

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p53 mediates Bcl-2 phosphorylation and apoptosis via activation of the Cdc42/JNK1 pathway

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Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease

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Hepatitis C virus NSSA protein protects against TNF-α mediated apoptotic cell death

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