Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression
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. HM...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/5/1088 |
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| author | 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 |
| author_facet | 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 |
| author_sort | I-Han Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T20:12:31Z |
| format | Article |
| id | doaj.art-7fb26b4cbd2946ffad065e40a0e0295f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:12:31Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7fb26b4cbd2946ffad065e40a0e0295f2023-11-19T22:51:17ZengMDPI AGCancers2072-66942020-04-01125108810.3390/cancers12051088Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer ProgressionI-Han Wang0Tzu-Ting Huang1Ji-Lin Chen2Li-Wei Chu3Yueh-Hsin Ping4Kai-Wen Hsu5Kuo-Hung Huang6Wen-Liang Fang7Hsin-Chen Lee8Chian-Feng Chen9Chen-Chung Liao10Rong-Hong Hsieh11Tien-Shun Yeh12Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 112, TaiwanInstitute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei 112, TaiwanInstitute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei 112, TaiwanDepartment and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, TaiwanDepartment and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, TaiwanResearch Center for Tumor Medical Science, China Medical University, Taichung 404, TaiwanInstitute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 112, TaiwanInstitute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 112, TaiwanDepartment and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, TaiwanCancer Progression Research Center, National Yang-Ming University, Taipei 112, TaiwanProteomics Research Center, National Yang-Ming University, Taipei 112, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110, TaiwanInstitute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei 112, TaiwanThe 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.https://www.mdpi.com/2072-6694/12/5/1088HMGCS1mevalonate pathwaygastric cancer progressionintegrated stress responsepluripotency |
| spellingShingle | 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 Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression Cancers HMGCS1 mevalonate pathway gastric cancer progression integrated stress response pluripotency |
| title | Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression |
| title_full | Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression |
| title_fullStr | Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression |
| title_full_unstemmed | Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression |
| title_short | Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression |
| title_sort | mevalonate pathway enzyme hmgcs1 contributes to gastric cancer progression |
| topic | HMGCS1 mevalonate pathway gastric cancer progression integrated stress response pluripotency |
| url | https://www.mdpi.com/2072-6694/12/5/1088 |
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