title: BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism.
abstract: Previously, we have identified the branched chain amino-acid transaminase 1 (BCAT1) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Knockdown of the BCAT1 expression in epithelial ovarian cancer (EOC) cells led to sharp decrease of cell proliferation, migration and invasion and inhibited cell cycle progression. BCAT1 silencing was associated with the suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Moreover, BCAT1 suppression resulted in downregulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism. Further metabolomic analyses were indicative for significant depletion of most amino acids and different phospho- and sphingolipids following BCAT1 knockdown. Finally, BCAT1 suppression led to significantly prolonged survival time in xenograft model of advanced peritoneal EOC. Taken together, our findings provide new insights about the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target.
authors.affiliation: Department of Molecular Medicine, Laval University, Québec PQ, Canada.|Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec PQ, Canada.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wang
authors.affiliation: Department of Molecular Medicine, Laval University, Québec PQ, Canada.|Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec PQ, Canada.
authors.forename: Adnen
authors.initials: A
authors.lastname: Faddaoui
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec PQ, Canada.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bachvarova
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec PQ, Canada.|Department of Obstetrics and Gynecology, Laval University, Québec PQ, Canada.
authors.forename: Marie
authors.initials: M
authors.lastname: Plante
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec PQ, Canada.|Department of Obstetrics and Gynecology, Laval University, Québec PQ, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Gregoire
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec PQ, Canada.|Department of Obstetrics and Gynecology, Laval University, Québec PQ, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Renaud
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec PQ, Canada.|Department of Obstetrics and Gynecology, Laval University, Québec PQ, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sebastianelli
authors.affiliation: Centre de recherche du CHU de Québec, CHUL, Québec PQ, Canada.|Faculty of Pharmacy, Laval University, Québec PQ, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Guillemette
authors.affiliation: Department of Molecular Medicine, Laval University, Québec PQ, Canada.|Centre de recherche du CHU de Québec, CHUL, Québec PQ, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gobeil
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macdonald
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Vanderhyden
authors.affiliation: Department of Molecular Medicine, Laval University, Québec PQ, Canada.|Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Québec PQ, Canada.
authors.forename: Dimcho
authors.initials: D
authors.lastname: Bachvarov
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D055432:Metabolomics; D016513:Mice, SCID; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D046888:Tissue Array Analysis; D000637:Transaminases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; C490590:BCAT1 protein, human; D000637:Transaminases
keywords: BCAT1; DNA hypomethylation; cancer metabolism; metastasis; ovarian cancer