Targeting the methionine-methionine adenosyl transferase 2A-S-adenosyl methionine axis for cancer therapy

Article Biochemistry & Molecular Biology

Methionine affects the expression of pluripotency genes and protein levels associated with methionine metabolism in adult, fetal, and cancer stem cells

Ozlem Altundag et al.

Summary: Methionine plays a critical role in the activity, self-renewal, and gene expression of stem cells. Different types of stem cells have varying responses to methionine metabolism, as well as differences in epigenetic regulation.

JOURNAL OF CELLULAR BIOCHEMISTRY (2022)

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Article Biochemistry & Molecular Biology

A guide to plasma membrane solute carrier proteins

Mattia D. Pizzagalli et al.

Summary: This review provides an overview of the SLC superfamily of transporter proteins and their roles in regulating metabolism and environmental conditions at the cell surface, with a focus on their involvement in cancer development and progression.

FEBS JOURNAL (2021)

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Article Oncology

MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage

Peter Kalev et al.

Summary: In MTAP-deleted cancers, potent MAT2A inhibitors were found to reduce SAM levels and decrease PRMT5 activity, leading to transcriptional perturbations that cause DNA damage and mitotic defects. This provides a rationale for combining MAT2A inhibitors with anti-mitotic drugs for treatment.

CANCER CELL (2021)

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Article Oncology

Cancer Dependencies: PRMT5 and MAT2A in MTAP/p16-Deleted Cancers

Katya Marjon et al.

Summary: Discovery of targeted therapies exploiting genetic inactivation of specific tumor suppressors, such as MTAP deletion, remains a challenge. However, inhibiting PRMT5 and MAT2A presents a precision medicine approach for these tumors with MTAP loss.

ANNUAL REVIEW OF CANCER BIOLOGY, VOL 5, 2021 (2021)

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Article Multidisciplinary Sciences

Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma

Man Hsin Hung et al.

Summary: The study reveals a correlation between T-cell exhaustion and overall survival in hepatocellular carcinoma patients, suggesting a link to oncogenic reprogramming of methionine metabolism. Reprogramming tumor methionine metabolism could be a potential therapeutic strategy to enhance HCC immunity.

NATURE COMMUNICATIONS (2021)

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Article Oncology

Combination Methionine-methylation-axis Blockade: A Novel Approach to Target the Methionine Addiction of Cancer

Takashi Higuchi et al.

Summary: The study demonstrated the efficacy of MET-methylation-axis blockade in a refractory cancer model, suggesting a promising strategy for cancer treatment.

CANCER GENOMICS & PROTEOMICS (2021)

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Article Chemistry, Medicinal

Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous MTAP Deletion

Zenon Konteatis et al.

Summary: This study reports the discovery of highly potent, selective MAT2A inhibitors that overcome previous challenges in targeting MAT2A. Through fragment screening and structure-guided design, these inhibitors significantly reduce SAM levels in cancer cells and selectively block proliferation of MTAP-null cells.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Chemistry, Medicinal

Fragment-Based Design of a Potent MAT2a Inhibitor and in Vivo Evaluation in an MTAP Null Xenograft Model

Claudia De Fusco et al.

Summary: MAT2a is an enzyme that synthesizes the essential metabolite SAM, making it an attractive target for treating MTAP-deleted cancers sensitive to its inhibition. Through structure-guided design and systematic SAR exploration, a potent series of MAT2a inhibitors has been developed, demonstrating promising antitumor response in in vivo studies.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Biochemistry & Molecular Biology

mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis

Elodie Villa et al.

Summary: mTORC1 regulates m(6)A RNA modification by controlling MAT2A and WTAP levels to promote protein synthesis and cell growth.

MOLECULAR CELL (2021)

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Article Multidisciplinary Sciences

Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia

Eliza Yankova et al.

Summary: The study identified a highly potent and selective catalytic inhibitor of METTL3, STM2457, which shows potential therapeutic value in treating AML. Treatment with this inhibitor leads to reduced AML growth, increased differentiation and apoptosis, and decreased m(6)A levels on leukemogenic mRNAs. In vivo pharmacological inhibition of METTL3 results in impaired engraftment and prolonged survival in mouse models of AML.

NATURE (2021)

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Article Biochemistry & Molecular Biology

MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients

Pei-Yi Chu et al.

Summary: The methionine cycle plays a crucial role in cancer cell proliferation and metabolic reprogramming. High levels of MAT2A in breast cancer patients are associated with worse survival rates, while an elevated MAT2A C/N ratio indicates increased invasiveness in breast cancer cells, making it a potential independent prognostic marker.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemistry & Molecular Biology

A comprehensive review of m6A/m6Am RNA methyltransferase structures

Stephanie Oerum et al.

Summary: Gene expression is regulated through various levels, including chemical modifications on RNA during or after transcription. One such modification is N6-methylation, which affects the structure, stability, degradation, and cellular interactions of the modified RNA, with dysregulation linked to multiple human cancers.RNA methyltransferases are the enzymes responsible for these modifications, and structural characterization of these enzymes is critical for understanding their functions.

NUCLEIC ACIDS RESEARCH (2021)

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Review Cell Biology

Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends

Kunal Nepali et al.

Summary: Research in epigenetic drug discovery has advanced significantly, with efforts focused on developing treatment strategies and utilizing emerging technologies like PROTACS and CRISPR/Cas9. Multi-targeting scaffold assemblies have been proposed as potential alternatives to combination therapy.

JOURNAL OF BIOMEDICAL SCIENCE (2021)

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Review Biochemistry & Molecular Biology

The role of m6A modification in the biological functions and diseases

Xiulin Jiang et al.

Summary: This paper highlights the importance of m6A RNA modification in eukaryotic RNA, including the roles of m6A methyltransferases, demethylases, and binding proteins. It emphasizes the crucial role of m6A RNA modification in the development of human cancers and discusses its impact on the physiological and pathological progressions of hematopoietic, central nervous, and reproductive systems.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Multidisciplinary Sciences

Enzyme-mediated depletion of serum L-Met abrogates prostate cancer growth via multiple mechanisms without evidence of systemic toxicity

Wei-Cheng Lu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Oncology

MAT2A as Key Regulator and Therapeutic Target in MLLr Leukemogenesis

Kathy-Ann Secker et al.

CANCERS (2020)

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Article Multidisciplinary Sciences

Cancer SLC43A2 alters T cell methionine metabolism and histone methylation

Yingjie Bian et al.

NATURE (2020)

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Review Cell Biology

PRMT5 function and targeting in cancer

Hyungsoo Kim et al.

CELL STRESS (2020)

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Review Oncology

CD8+ T cell states in human cancer: insights from single-cell analysis

Anne M. Van der Leun et al.

NATURE REVIEWS CANCER (2020)

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Article Oncology

S-adenosylmethionine biosynthesis is a targetable metabolic vulnerability of cancer stem cells

Elena Strekalova et al.

BREAST CANCER RESEARCH AND TREATMENT (2019)

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Article Biochemistry & Molecular Biology

Methionine is a metabolic dependency of tumor-initiating cells

Zhenxun Wang et al.

NATURE MEDICINE (2019)

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Article

MicroRNA-203 impacts on the growth, aggressiveness and prognosis of hepatocellular carcinoma by targeting MAT2A and MAT2B genes

Maria M. Simile et al.

Oncotarget (2019)

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Meeting Abstract Oncology

Targeting MAT2A in CDKN2A/MTAP-deleted cancers

Katya Marjon et al.

CANCER RESEARCH (2019)

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Review Biochemistry & Molecular Biology

Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials

Yuan Cheng et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2019)

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Article Biochemistry & Molecular Biology

Balance between MAT2A intron detention and splicing is determined cotranscriptionally

Kathryn E. Pendleton et al.

RNA (2018)

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Article Biochemistry & Molecular Biology

Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A

Casey L. Quinlan et al.

NATURE CHEMICAL BIOLOGY (2017)

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Article Cell Biology

Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome-Scale Network Modeling

Sriram Chandrasekaran et al.

CELL REPORTS (2017)

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Article Biochemistry & Molecular Biology

The U6 snRNA m6A Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention

Kathryn E. Pendleton et al.

CELL (2017)

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Article Multidisciplinary Sciences

Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos

Xiaoyu Liu et al.

NATURE (2016)

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Article Multidisciplinary Sciences

Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes

Ben Murray et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

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Review Genetics & Heredity

H3K9me3-Dependent Heterochromatin: Barrier to Cell Fate Changes

Justin S. Becker et al.

TRENDS IN GENETICS (2016)

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Article Cell Biology

MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis

Katya Marjon et al.

CELL REPORTS (2016)

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Review Neurosciences

A Comprehensive View of the Epigenetic Landscape. Part II: Histone Post-translational Modification, Nucleosome Level, and Chromatin Regulation by ncRNAs

Anna Sadakierska-Chudy et al.

NEUROTOXICITY RESEARCH (2015)

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Article Cell Biology

Methionine Metabolism Regulates Maintenance and Differentiation of Human Pluripotent Stem Cells

Nobuaki Shiraki et al.

CELL METABOLISM (2014)

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Article Chemistry, Medicinal

2′,6′-Dihalostyrylanilines, Pyridines, and Pyrimidines for the Inhibition of the Catalytic Subunit of Methionine S-Adenosyltransferase-2

Vitaliy M. Sviripa et al.

JOURNAL OF MEDICINAL CHEMISTRY (2014)

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Review Neurosciences

DNA Methylation and Its Basic Function

Lisa D. Moore et al.

NEUROPSYCHOPHARMACOLOGY (2013)

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Review Biochemistry & Molecular Biology

DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer

P. Lopez-Serra et al.

ONCOGENE (2012)

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Review Ecology

Epigenetics and gene expression

E. R. Gibney et al.

HEREDITY (2010)

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Review Endocrinology & Metabolism

Minireview: Protein Arginine Methylation of Nonhistone Proteins in Transcriptional Regulation

Young-Ho Lee et al.

MOLECULAR ENDOCRINOLOGY (2009)

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Review Biochemistry & Molecular Biology

S-Adenosyl-L-methionine:: Beyond the universal methyl group donor

Sanja Roje

PHYTOCHEMISTRY (2006)

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Review Genetics & Heredity

DNA hypermethylation: when tumour suppressor genes go silent

GA Garinis et al.

HUMAN GENETICS (2002)

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Article Biochemistry & Molecular Biology

Homocysteine

JD Finkelstein et al.

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY (2000)

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Targeting the methionine-methionine adenosyl transferase 2A-S-adenosyl methionine axis for cancer therapy

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