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
  • 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: [email protected].
  • 5. State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China. Electronic address: [email protected].
  • 6. Department of Nutrition and Food Hygiene, School of Public Health, Medical College of Soochow University, Suzhou, China. Electronic address: [email protected].
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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