Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression

Autor: 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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cancers, Vol 12, Iss 5, p 1088 (2020)
Druh dokumentu: article
ISSN: 2072-6694
DOI: 10.3390/cancers12051088
Popis: 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.
Databáze: Directory of Open Access Journals
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