Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice

• Published in: International journal of molecular sciences 2019-10, Vol.20 (20), p.4983
• Main Authors: Martin, Kelly A, Hum, Nicholas R, Sebastian, Aimy, He, Wei, Siddiqui, Salma, Ghosh, Paramita M, Pan, Chong-Xian, de Vere White, Ralph, Loots, Gabriela G
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Antineoplastic Agents - pharmacology; Biological and medical sciences; Bladder cancer; Cancer; Cancer therapies; Cell Line, Tumor; Cell Proliferation; Cell Survival - drug effects; Cell Survival - genetics; Chemotherapy; Cisplatin; Disease Models, Animal; DNA methylation; Drug resistance; Drug Resistance, Neoplasm - genetics; Gemcitabine; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunological tolerance; Metabolism; Methionine; Methionine adenosyltransferase; Methionine Adenosyltransferase - genetics; Methionine Adenosyltransferase - metabolism; methyltransferase; Mice; Molecular modelling; Ontology; Patients; Phosphorylation; Protein expression; Proteins; Sequence analysis; Transcriptome; Transcriptomics; Tumors; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - mortality; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20204983

Bladder cancer is among the top ten most common cancers, with about ~380,000 new cases and ~150,000 deaths per year worldwide. Tumor relapse following chemotherapy treatment has long been a significant challenge towards completely curing cancer. We have utilized a patient-derived bladder cancer xenograft (PDX) platform to characterize molecular mechanisms that contribute to relapse following drug treatment in advanced bladder cancer. Transcriptomic profiling of bladder cancer xenograft tumors by RNA-sequencing analysis, before and after relapse, following a 21-day cisplatin/gemcitabine drug treatment regimen identified methionine adenosyltransferase 1a ( ) as one of the significantly upregulated genes following drug treatment. Survey of patient tumor sections confirmed elevated levels of in individuals who received chemotherapy. Overexpression of in 5637 bladder cancer cells increased tolerance to gemcitabine and stalled cell proliferation rates, suggesting upregulation as a potential mechanism by which bladder cancer cells persist in a quiescent state to evade chemotherapy.