S1PR3 inhibition impairs cell cycle checkpoint via the AKT/WEE1 pathway in oral squamous cell carcinoma

Xinxia Zhou1, Jinghao Liu1, Xu Chen1

  • 1Department of Clinical Immunology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Abstract

Insights

Sphingosine-1-phosphate receptor 3 (S1PR3) promotes oral cancer growth by disrupting the cell cycle. Targeting S1PR3 inhibits tumor progression and enhances cisplatin effectiveness in oral squamous cell carcinoma (OSCC) treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Sphingosine-1-phosphate receptor 3 (S1PR3) is implicated in various cancers.
  • Its specific role and mechanisms in oral squamous cell carcinoma (OSCC) are not well understood.

Purpose of the Study:

  • Investigate the function of S1PR3 in OSCC progression.
  • Evaluate S1PR3 as a potential therapeutic target for OSCC.

Main Methods:

  • Assessed S1PR3 expression using qPCR, Western blotting, IHC, and TCGA data.
  • Analyzed S1PR3's impact on OSCC proliferation, cell cycle, and prognosis.
  • Explored molecular mechanisms via RNA-seq and cell cycle arrays.
  • Tested combination therapy with an S1PR3 antagonist and cisplatin.

Main Results:

  • S1PR3 is overexpressed in OSCC, correlating with poor prognosis.
  • Targeting S1PR3 reduced AKT/WEE1/CDC2 phosphorylation, inhibiting cell cycle progression.
  • S1PR3 inhibition disrupted the G2/M checkpoint and suppressed OSCC proliferation.
  • Combined S1PR3 antagonist and cisplatin showed synergistic anti-tumor effects.

Conclusions:

  • S1PR3 critically regulates the OSCC cell cycle through the AKT/WEE1/CDC2 pathway.
  • S1PR3 represents a promising therapeutic target for OSCC treatment.
  • Combination therapy may enhance treatment efficacy for OSCC patients.

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