Mevalonate pathway enzyme HMGCS1 contributes to gastric cancer progression

I. Han Wang, Tzu Ting Huang, Ji Lin Chen, Li Wei Chu, Yueh Hsin Ping, Kai Wen Hsu, Kuo Hung Huang, Wen Liang Fang, Hsin Chen Lee, Chian Feng Chen, Chen Chung Liao, Rong Hong Hsieh, Tien Shun Yeh

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1 Citation (Scopus)

Abstract

The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.

Original languageEnglish
Article number1088
JournalCancers
Volume12
Issue number5
DOIs
Publication statusPublished - May 2020

Keywords

  • Gastric cancer progression
  • HMGCS1
  • Integrated stress response
  • Mevalonate pathway
  • Pluripotency

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Wang, I. H., Huang, T. T., Chen, J. L., Chu, L. W., Ping, Y. H., Hsu, K. W., Huang, K. H., Fang, W. L., Lee, H. C., Chen, C. F., Liao, C. C., Hsieh, R. H., & Yeh, T. S. (2020). Mevalonate pathway enzyme HMGCS1 contributes to gastric cancer progression. Cancers, 12(5), [1088]. https://doi.org/10.3390/cancers12051088