AKT1 regulates UHRF1 protein stability and promotes the resistance to abiraterone in prostate cancer

Article Cell Biology

Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function

Xiang Xu et al.

Summary: The study reveals that UHRF1 acts as a novel gate-keeper of AMPK, regulating cellular energy metabolism and playing critical roles in glucose and lipid metabolism.

CELL RESEARCH (2022)

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Review Medicine, General & Internal

Overview of the Development and Use of Akt Inhibitors in Prostate Cancer

Anis Gasmi et al.

Summary: Deregulation of the PI3K-Akt-mTOR pathway is crucial in the development and progression of various cancers. In prostate cancer, PTEN loss of function is believed to be the main driver. Despite the challenges in developing selective Akt inhibitors, recent phase II and III clinical trials have shown promising outcomes with Ipatasertib and Capivasertib in combination with androgen deprivation therapies for patients with metastatic castration-resistant prostate cancer and PTEN loss. Ongoing trials are currently evaluating different combinations of Akt inhibitors at different stages of prostate cancer.

JOURNAL OF CLINICAL MEDICINE (2022)

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Review Pharmacology & Pharmacy

Targeting Akt/PKB in pediatric tumors: A review from preclinical to clinical trials

Bruno Toson et al.

Summary: This article reviews the application of Akt inhibitors in pediatric cancers. The study demonstrates the impact of Akt inhibition on tumorigenesis and suggests targeting the PI3K/Akt/mTOR signaling pathway as an effective approach for treating pediatric tumors.

PHARMACOLOGICAL RESEARCH (2022)

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Article Oncology

UHRF1 overexpression promotes osteosarcoma metastasis through altered exosome production and AMPK/SEMA3E suppression

Stephanie C. Wu et al.

Summary: Loss-of-function mutations at the RB1 gene worsen clinical outcomes in osteosarcoma. The study has identified UHRF1 as an important downstream effector of the RB/E2F signaling pathway that promotes cell proliferation, migration, invasion, angiogenesis, and metastasis in osteosarcoma. UHRF1 overexpression suppresses AMPK activation and SEMA3E expression, leading to increased angiogenesis. Additionally, UHRF1 affects the expression of extracellular vesicles and their cargo, including uPA, contributing to migration and metastasis. Knocking out Uhrf1 in a mouse model shows decreased metastasis and improved survival in RB1 loss-associated osteosarcoma.

ONCOGENESIS (2022)

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Article Oncology

UHRF1 promotes androgen receptor-regulated CDC6 transcription and anti-androgen receptor drug resistance in prostate cancer through KDM4C-Mediated chromatin modifications

Yingxue Gao et al.

Summary: UHRF1 and CDC6, oncogenes that play critical roles in therapeutic resistance, are upregulated simultaneously in prostate cancer, where UHRF1 promotes CDC6 transcription controlled by AR through chromatin modification, contributing to anti-AR drug resistance and worse survival. Targeting both AR and UHRF1 simultaneously could be a novel and promising therapeutic approach for prostate cancer.

CANCER LETTERS (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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Review Oncology

Targeting Akt in cancer for precision therapy

Hui Hua et al.

Summary: Biomarkers-guided precision therapeutics has revolutionized the clinical development and administration of molecular-targeted anticancer agents. Tailored precision cancer therapy exhibits better response rate compared to unselective treatment. Protein kinases have critical roles in cell signaling, metabolism, proliferation, survival and migration. Aberrant activation of protein kinases is critical for tumor growth and progression. Consequently, protein kinases are key targets for molecular targeted cancer therapy. The serine/threonine kinase Akt is frequently activated in various types of cancer. Activation of Akt promotes tumor progression and drug resistance. Since the first Akt inhibitor was reported in 2000, many Akt inhibitors have been developed and evaluated in either early or late stage of clinical trials, which take advantage of liquid biopsy and genomic or molecular profiling to realize personalized cancer therapy. Two inhibitors, capivasertib and ipatasertib, are being tested in phase III clinical trials for cancer therapy. This article highlights recent progress of Akt signaling pathway, reviews the up-to-date data from clinical studies of Akt inhibitors and discusses the potential biomarkers that may help personalized treatment of cancer with Akt inhibitors. Additionally, it also discusses how Akt may confer the vulnerability of cancer cells to some kinds of anticancer agents.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Article Biochemistry & Molecular Biology

Serine 298 Phosphorylation in Linker 2 of UHRF1 Regulates Ligand-Binding Property of Its Tandem Tudor Domain

Satomi Kori et al.

JOURNAL OF MOLECULAR BIOLOGY (2020)

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Review Biochemistry & Molecular Biology

The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling

Boris Y. Shorning et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Endocrinology & Metabolism

Targeting prosurvival BCL2 signaling through Akt blockade sensitizes castration-resistant prostate cancer cells to enzalutamide

Amanda B. Pilling et al.

PROSTATE (2019)

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Article Medicine, Research & Experimental

N-Myc mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer

Adeline Berger et al.

JOURNAL OF CLINICAL INVESTIGATION (2019)

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Review Oncology

Neuroendocrine Differentiation of Prostate Cancer-An Intriguing Example of Tumor Evolution at Play

Girijesh Kumar Patel et al.

CANCERS (2019)

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Article Biochemistry & Molecular Biology

Methylation of UHRF1 by SET7 is essential for DNA double-strand break repair

Ja Young Hahm et al.

NUCLEIC ACIDS RESEARCH (2019)

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Article Oncology

Heterochromatin Protein 1α Mediates Development and Aggressiveness of Neuroendocrine Prostate Cancer

Xinpei Ci et al.

CANCER RESEARCH (2018)

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Article Genetics & Heredity

The long tail of oncogenic drivers in prostate cancer

Joshua Armenia et al.

NATURE GENETICS (2018)

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Article Cell Biology

FOXM1 contributes to taxane resistance by regulating UHRF1-controlled cancer cell stemness

Bowen Yuan et al.

CELL DEATH & DISEASE (2018)

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Article Multidisciplinary Sciences

Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance

Sheng Yu Ku et al.

SCIENCE (2017)

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Review Oncology

AR Signaling and the PI3K Pathway in Prostate Cancer

Megan Crumbaker et al.

CANCERS (2017)

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Article Biochemistry & Molecular Biology

The PI3K AKT pathway in the pathogenesis of prostate cancer

Xiaofei Wen

Frontiers in Bioscience-Landmark (2016)

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Article Multidisciplinary Sciences

A cell cycle-dependent BRCA1-UHRF1 cascade regulates DNA double-strand break repair pathway choice

Haoxing Zhang et al.

NATURE COMMUNICATIONS (2016)

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Article Biochemistry & Molecular Biology

Targeting the MLL complex in castration-resistant prostate cancer

Rohit Malik et al.

NATURE MEDICINE (2015)

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Review Urology & Nephrology

Are androgen receptor variants a substitute for the full-length receptor?

Ji Lu et al.

NATURE REVIEWS UROLOGY (2015)

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Article Cell Biology

UHRF1 Contributes to DNA Damage Repair as a Lesion Recognition Factor and Nuclease Scaffold

Yanyan Tian et al.

CELL REPORTS (2015)

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Article Oncology

Rottlerin induces autophagy and apoptosis in prostate cancer stem cells via PI3K/Akt/mTOR signaling pathway

Dhruv Kumar et al.

CANCER LETTERS (2014)

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Article Oncology

AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer

Carmen Priolo et al.

CANCER RESEARCH (2014)

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Article Biochemistry & Molecular Biology

DNA Damage Regulates UHRF1 Stability via the SCFβ-TrCP E3 Ligase

Hao Chen et al.

MOLECULAR AND CELLULAR BIOLOGY (2013)

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Article Biochemistry & Molecular Biology

Depletion of Uhrf1 inhibits chromosomal DNA replication in Xenopus egg extracts

Elaine M. Taylor et al.

NUCLEIC ACIDS RESEARCH (2013)

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Article Oncology

Non-metastatic CRPC and asymptomatic metastatic CRPC: which treatment for which patient?

B. Tombal

ANNALS OF ONCOLOGY (2012)

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Article Biochemistry & Molecular Biology

UHRF1 Double Tudor Domain and the Adjacent PHD Finger Act Together to Recognize K9me3-Containing Histone H3 Tail

Si Xie et al.

JOURNAL OF MOLECULAR BIOLOGY (2012)

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Article Cell Biology

UHRF1 phosphorylation by cyclin A2/cyclin-dependent kinase 2 is required for zebrafish embryogenesis

Jaime Chu et al.

MOLECULAR BIOLOGY OF THE CELL (2012)

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Article Medicine, General & Internal

Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy

Howard I. Scher et al.

NEW ENGLAND JOURNAL OF MEDICINE (2012)

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Article Biochemistry & Molecular Biology

The SRA protein UHRF1 promotes epigenetic crosstalks and is involved in prostate cancer progression

F. Babbio et al.

ONCOGENE (2012)

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Article Multidisciplinary Sciences

M phase phosphorylation of the epigenetic regulator UHRF1 regulates its physical association with the deubiquitylase USP7 and stability

Honghui Ma et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2012)

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Article Urology & Nephrology

Prostate cancer epidemiology in the United States

Otis W. Brawley

WORLD JOURNAL OF UROLOGY (2012)

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Article Biochemistry & Molecular Biology

UHRF1 depletion causes a G2/M arrest, activation of DNA damage response and apoptosis

Amy L. Tien et al.

BIOCHEMICAL JOURNAL (2011)

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Article Oncology

Cell Autonomous Role of PTEN in Regulating Castration-Resistant Prostate Cancer Growth

David J. Mulholland et al.

CANCER CELL (2011)

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Article Medicine, General & Internal

Abiraterone and Increased Survival in Metastatic Prostate Cancer

Johann S. De Bono et al.

NEW ENGLAND JOURNAL OF MEDICINE (2011)

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Article Oncology

UHRF1 is a novel diagnostic marker of lung cancer

M. Unoki et al.

BRITISH JOURNAL OF CANCER (2010)

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Article Oncology

UHRF1 is a novel molecular marker for diagnosis and the prognosis of bladder cancer

M. Unoki et al.

BRITISH JOURNAL OF CANCER (2009)

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Article Biochemistry & Molecular Biology

UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications

Hideharu Hashimoto et al.

EPIGENETICS (2009)

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Article Biochemistry & Molecular Biology

UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells

Jong Kyong Kim et al.

NUCLEIC ACIDS RESEARCH (2009)

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Review Urology & Nephrology

Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion

William P. Harris et al.

NATURE CLINICAL PRACTICE UROLOGY (2009)

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AKT1 regulates UHRF1 protein stability and promotes the resistance to abiraterone in prostate cancer

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