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

Wang, Zhiqiang; Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Grégoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Guillemette, Chantal; Gobeil, Stéphane; Macdonald, Elizabeth; Vanderhyden, Barbara C.; Bachvarov, Dimcho

doi:10.18632/oncotarget.5159

Cited by 90 publications

(92 citation statements)

References 98 publications

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“…BCAAs degradation is regulated by the BCAT1 and BCAT2 enzymes [34]. We have recently shown that the suppression of the BCAT1 gene in EOC cells resulted in the down-regulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism [56]. Our data suggest a similar effect imposed by the suppression of the GALNT3 gene.…”

Section: Discussionsupporting

confidence: 60%

A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells

Sheta

Woo

Roux‐Dalvai³

et al. 2016

Journal of Proteomics

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Epithelial ovarian cancer (EOC) is a disease responsible for more deaths among women in the Western world than all other gynecologic malignancies. There is urgent need for new therapeutic targets and a better understanding of EOC initiation and progression. We have previously identified the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene, a member of the GalNAc-transferases (GalNAc-Ts) gene family, as hypomethylated and overexpressed in high-grade serous EOC tumors, compared to low malignant potential EOC tumors and normal ovarian tissues. This data also suggested for a role of GALNT3 in aberrant EOC glycosylation, possibly implicated in disease progression. To evaluate differential glycosylation in EOC caused by modulations in GALNT3 expression, we used a metabolic labeling strategy for enrichment and mass spectrometry-based characterization of glycoproteins following GALNT3 gene knockdown (KD) in A2780s EOC cells. A total of 589 differentially expressed glycoproteins were identified upon GALNT3 KD. Most identified proteins were involved in mechanisms of cellular metabolic functions, post-translational modifications, and some have been reported to be implicated in EOC etiology. The GALNT3-dependent glycoproteins identified by this metabolic labeling approach support the oncogenic role of GALNT3 in EOC dissemination and may be pursued as novel EOC biomarkers and/or therapeutic targets. Biological significance: Knowledge of the O-glycoproteome has been relatively elusive, and the functions of the individual polypeptide GalNAc-Ts have been poorly characterized. Alterations in GalNAc-Ts expression were shown to provide huge variability in the O-glycoproteome in various pathologies, including cancer. The application of a chemical biology approach for the metabolic labeling and subsequent characterization of O-glycoproteins in EOC using the Ac4GalNAz metabolite has provided a strategy allowing for proteomic discovery of GalNAc-Ts specific functions. Our study supports an essential role of one of the GalNAc-Ts — GALNT3, in EOC dissemination, including its implication in modulating PTMs and EOC metabolism. Our approach validates the use of the applied metabolic strategy to identify important functions of GalNAc-Ts in normal and pathological conditions.

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Section: Discussionsupporting

confidence: 60%

A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells

Sheta

Woo

Roux‐Dalvai³

et al. 2016

Journal of Proteomics

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“…For example, GPNMB/OA increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP2 and MMP9 activities, and also enhances tumorigenesis of human lung cancer and breast cancer PRRX1 promotes epithelial‐mesenchymal transition (EMT) through the Wnt/b‐catenin pathway in gastric cancer and also has been identified as a new EMT inducer in breast and colorectal cancer . Similarly, overexpression of BCAT1 , a c‐Myc target gene might associate with ovarian cancer progression and induce cell proliferation, migration and invasion in nasopharyngeal carcinoma . Some in vitro trials indicated that suppression of BCAT1 could significantly decrease tumour proliferation in glioma cell lines .…”

Section: Discussionmentioning

confidence: 99%

In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer

Wei

Wong

Lyu

et al. 2018

J Cellular Molecular Medi

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Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progression; however, the mechanism of OPN‐induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage‐independent growth, cell migration and invasion in KRAS gene mutant cells but to a lesser extent in KRAS wild‐type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E‐cadherin in KRAS mutant cells. In human CRC specimens, a high‐level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E‐cadherin expression. Furthermore, we have found that 15 genes were co‐upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene signature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer.

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“…The cell lines were passed in different culture media supplemented with 10% fetal bovine serum, as described previously. 65,67 Bisulfite sequencing PCR (BSP) analysis BSP analysis was performed, as described previously. 65,67 Briefly, genomic DNA extracted from EOC tumors and control ovarian tissues was isolated using the Qiagen DNeasy Blood and Tissue Kit.…”

Section: Cell Culturesmentioning

confidence: 99%

Suppression of the grainyhead transcription factor 2 gene (GRHL2) inhibits the proliferation, migration, invasion and mediates cell cycle arrest of ovarian cancer cells

et al. 2017

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Previously, we have identified the Grainyhead transcription factor 2 gene (GRHL2) as notably hypomethylated in high-grade (HG) serous epithelial ovarian tumors, compared with normal ovarian tissues. GRHL2 is known for its functions in normal tissue development and wound healing. In the context of cancer, the role of GRHL2 is still ambiguous as both tumorigenic and tumor suppressive functions have been reported for this gene, although a role of GRHL2 in maintaining the epithelial status of cancer cells has been suggested. In this study, we report that GRHL2 is strongly overexpressed in both low malignant potential (LMP) and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Suppression of the GRHL2 expression led to a sharp decrease in cell proliferation, migration and invasion and induced G1 cell cycle arrest in epithelial ovarian cancer (EOC) cells displaying either epithelial (A2780s) or mesenchymal (SKOV3) phenotypes. However, no phenotypic alterations were observed in these EOC cell lines following GRHL2 silencing. Gene expression profiling and consecutive canonical pathway and network analyses confirmed these data, as in both these EOC cell lines, GRHL2 ablation was associated with the downregulation of various genes and pathways implicated in cell growth and proliferation, cell cycle control and cellular metabolism. Taken together, our data are indicative for a strong oncogenic potential of the GRHL2 gene in EOC progression and support recent findings on the role of GRHL2 as one of the major phenotypic stability factors (PSFs) that stabilize the highly aggressive/metastatic hybrid epithelial/mesenchymal (E/M) phenotype of cancer cells.

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

Cited by 90 publications

References 98 publications

A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells

A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells

In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer

Suppression of the grainyhead transcription factor 2 gene (GRHL2) inhibits the proliferation, migration, invasion and mediates cell cycle arrest of ovarian cancer cells

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