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S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1/2-YAP pathway

Yi-Ping Tao1, Heng-Yan Zhu1, Qian-Yuan Shi1

  • 1Department of Cell Biology, College of Medicine, Jiaxing University, 118 Jiahang Road, Jiaxing, 314001, China.

Oncogene
|October 12, 2023
PubMed

Insights

Targeting Sphingosine-1-phosphate receptor 1 (S1PR1) promotes ovarian cancer cell senescence and enhances chemotherapy response. This pathway involves S1PR1, PDK1, LATS1/2, and YAP, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cell senescence is a tumor-suppressive mechanism that halts cancer cell proliferation.
  • Sphingosine-1-phosphate receptor 1 (S1PR1) is implicated in various cancers, but its role in ovarian cancer cell senescence is unclear.
  • Understanding S1PR1's function in ovarian cancer is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To elucidate the mechanism by which S1PR1 regulates ovarian cancer cell senescence.
  • To investigate the potential of S1PR1 as a druggable target for ovarian cancer therapy.

Main Methods:

  • Analysis of S1PR1 expression in human ovarian cancer tissues and cell lines.
  • Functional studies involving S1PR1 deletion or knockout in ovarian cancer cells.
  • Investigation of the S1PR1-PDK1-LATS1/2-YAP signaling pathway using molecular and pharmacological approaches.
  • Chromatin immunoprecipitation to confirm transcriptional regulation.

Main Results:

  • S1PR1 is highly expressed in ovarian cancer and its deletion inhibits proliferation and migration.
  • S1PR1 deletion induces ovarian cancer cell senescence and sensitizes cells to cisplatin.
  • S1PR1 signaling regulates the PDK1-LATS1/2-YAP axis, involving a YAP-mediated feedback loop on S1PR1.
  • YAP transcriptionally regulates S1PR1 expression.

Conclusions:

  • The S1PR1-PDK1-LATS1/2-YAP pathway is a key regulator of ovarian cancer cell senescence via a YAP feedback loop.
  • S1PR1 is a druggable target for inducing senescence in ovarian cancer.
  • Targeting this pathway may enhance the efficacy of standard chemotherapy for ovarian cancer.

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