Oncotarget

Research Papers:

BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism

Zhi-Qiang Wang, Adnen Faddaoui, Magdalena Bachvarova, Marie Plante, Jean Gregoire, Marie-Claude Renaud, Alexandra Sebastianelli, Chantal Guillemette, Stéphane Gobeil, Elizabeth Macdonald, Barbara Vanderhyden and Dimcho Bachvarov _

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Oncotarget. 2015; 6:31522-31543. https://doi.org/10.18632/oncotarget.5159

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Abstract

Zhi-Qiang Wang1,2, Adnen Faddaoui1,2, Magdalena Bachvarova2, Marie Plante2,3, Jean Gregoire2,3, Marie-Claude Renaud2,3, Alexandra Sebastianelli2,3, Chantal Guillemette4,5, Stéphane Gobeil1,4, Elizabeth Macdonald6, Barbara Vanderhyden6, Dimcho Bachvarov1,2

1Department of Molecular Medicine, Laval University, Québec PQ, Canada

2Centre de recherche du CHU de Québec, L’Hôtel-Dieu de Québec, Québec PQ, Canada

3Department of Obstetrics and Gynecology, Laval University, Québec PQ, Canada

4Centre de recherche du CHU de Québec, CHUL, Québec PQ, Canada

5Faculty of Pharmacy, Laval University, Québec PQ, Canada

6Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada

Correspondence to:

Dimcho Bachvarov, e-mail: dimtcho.batchvarov@crhdq.ulaval.ca

Keywords: BCAT1, ovarian cancer, cancer metabolism, metastasis, DNA hypomethylation

Received: May 07, 2015     Accepted: August 28, 2015     Published: September 10, 2015

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.


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