HMGCS2 enhances invasion and metastasis via direct interaction with PPARα to activate Src signaling in colorectal cancer and oral cancer.

Shih-Wen Chen, Chiang-Ting Chou, Cheng-Chi Chang, Yue-Ju Li, Szu-Ta Chen, I-Ching Lin, Sang-Heng Kok, Shih-Jung Cheng, Jang-Jaer Lee, Tai-Sheng Wu, Min-Liang Kuo, Been-Ren Lin

Oncotarget 2017 Apr 04

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Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.

Citation

Shih-Wen Chen, Chiang-Ting Chou, Cheng-Chi Chang, Yue-Ju Li, Szu-Ta Chen, I-Ching Lin, Sang-Heng Kok, Shih-Jung Cheng, Jang-Jaer Lee, Tai-Sheng Wu, Min-Liang Kuo, Been-Ren Lin. HMGCS2 enhances invasion and metastasis via direct interaction with PPARα to activate Src signaling in colorectal cancer and oral cancer. Oncotarget. 2017 Apr 04;8(14):22460-22476