2. Academic Validation
  3. Activated PARP1/FAK/COL5A1 signaling facilitates the tumorigenesis of cholesterol-resistant ovarian cancer cells through promoting EMT

Activated PARP1/FAK/COL5A1 signaling facilitates the tumorigenesis of cholesterol-resistant ovarian cancer cells through promoting EMT

  • Cell Signal. 2024 Sep 16:124:111419. doi: 10.1016/j.cellsig.2024.111419.
Zeyin He 1,  Shiyi Gong 1,  Xu Zhang 1,  Jie Li 1,  Jinglin Xue 1,  Qi Zeng 1,  Jing Nie 2,  Zengli Zhang 3,  Hongmei Ding 4,  Hailong Pei 5,  Bingyan Li 6
Affiliations

Affiliations

  • 1 Department of Nutrition and Food Hygiene, School of Public Health, Medical College of Soochow University, Suzhou, China.
  • 2 State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China.
  • 3 Department of Occupational and Environmental Health, School of Public Health, Suzhou Medical College of Soochow University, Suzhou 215123, China.
  • 4 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Soochow University, Suzhou 215123, China. Electronic address: dinghongmei@suda.edu.cn.
  • 5 State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China. Electronic address: hlpei@suda.edu.cn.
  • 6 Department of Nutrition and Food Hygiene, School of Public Health, Medical College of Soochow University, Suzhou, China. Electronic address: bingyanli@suda.edu.cn.
PMID: 39293744 DOI: 10.1016/j.cellsig.2024.111419
Abstract

Cancer cells require plentiful Cholesterol for membrane biogenesis and other functional needs due to fast proliferating, leading to the interaction of Cholesterol or its metabolites with cancer-related pathways. However, the impact of long-lasting high Cholesterol concentrations on tumorigenesis and its underlying mechanisms remains largely unexplored. To the best of our knowledge, this study is the first to establish a cholesterol-resistant ovarian Cancer cells, whose intracellular total Cholesterol level up to 6-8 mmol/L. We confirmed that high Cholesterol facilitated the progression of ovarian Cancer in vitro and in vivo. Notably, our findings revealed significant upregulation of collagen type V alpha 1 chain (COL5A1) expression in cholesterol-resistant ovarian Cancer cells and human ovarian Cancer tissue, which was depended on FAK/Src activation. Mechanistically, PARP1 directly bound to FAK in response to activate FAK/Src/COL5A1 signaling. Intriguingly, COL5A1 depletion significantly impeded the tumorigenesis of these cells, concomitant with a decrease in epithelial-mesenchymal transition (EMT) progression. In conclusion, PARP1/FAK/COL5A1 signaling activation facilitated progression of cholesterol-resistant ovarian Cancer cells by promoting EMT, thereby broadening a new therapeutic opportunity.

Keywords

COL5A1; Cholesterol resistance; EMT; Invasion; Ovarian cancer.

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