Oncotarget

Research Papers:

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 and Been-Ren Lin _

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Oncotarget. 2017; 8:22460-22476. https://doi.org/10.18632/oncotarget.13006

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Abstract

Shih-Wen Chen1,*, Chiang-Ting Chou2,3,*, Cheng-Chi Chang1,4,5,6,7,8, Yue-Ju Li4, Szu-Ta Chen9,10, I-Ching Lin11,12,13, Sang-Heng Kok14,15, Shih-Jung Cheng1,4,15, Jang-Jaer Lee7, Tai-Sheng Wu4, Min-Liang Kuo17, Been-Ren Lin16

1Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan

2Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan

3Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan

4Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan

5Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan

6Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

7Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

8Department of Biotechnology, Asia University, Taichung, Taiwan

9Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

10Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan

11School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

12Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan

13School of Medicine, Chung Shan Medical University, Taichung, Taiwan

14Division of Oral and Maxillofacial Surgery, Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan

15Department of Dentistry, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

16Department of Surgery, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

17Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

*These authors contributed equally to this work

Correspondence to:

Been-Ren Lin, email: beenrenlin@ntu.edu.tw

Keywords: HMGCS2, PPARα, metastasis, CRC, OSCC

Received: May 31, 2016     Accepted: October 21, 2016     Published: November 01, 2016

ABSTRACT

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.


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