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Protein S drives oral squamous cell carcinoma tumorigenicity through regulation of AXL

Ghada Abboud-Jarrous1, Shivam Priya1, Avi Maimon1

  • 1Institute for Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Israel.

Oncotarget
|January 25, 2017
PubMed

Insights

Protein S (PROS1) drives Oral Squamous Cell Carcinoma (OSCC) growth by regulating AXL receptor tyrosine kinase. Targeting PROS1 offers a potential new therapeutic strategy for OSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The TAM family of receptor tyrosine kinases (TYRO3, AXL, MERTK) are proto-oncogenes involved in cancer progression.
  • Mechanisms of TAM receptor activation in cancer remain incompletely understood.
  • Protein S (PROS1) has been identified as a ligand for TAM receptors.

Purpose of the Study:

  • To investigate the role of PROS1 in Oral Squamous Cell Carcinoma (OSCC).
  • To elucidate the functional relationship between PROS1 and TAM signaling, particularly AXL, in OSCC.
  • To evaluate PROS1 as a potential therapeutic target in OSCC.

Main Methods:

  • Utilized shRNA to knockdown PROS1 expression in OSCC cell lines.
  • Assessed effects of PROS1 manipulation on cell proliferation, migration, and anchorage-independent growth in vitro.
  • Evaluated tumor growth in xenograft models and analyzed AXL expression at transcriptional and protein levels.
  • Investigated the impact of PROS1 inhibition on the efficacy of the AXL inhibitor R428.

Main Results:

  • PROS1 overexpression enhanced OSCC proliferation and migration, while PROS1 knockdown significantly inhibited these processes.
  • PROS1 knockdown reduced tumor xenograft growth in vivo and altered cancer cell differentiation.
  • PROS1 regulates AXL expression at both transcriptional and protein levels in OSCC.
  • Inhibition of PROS1 diminished the anti-proliferative effects of an AXL inhibitor, highlighting functional crosstalk.

Conclusions:

  • PROS1 acts as a key mediator and driver of OSCC tumor growth.
  • PROS1 modulates AXL expression and signaling, impacting OSCC progression.
  • PROS1 represents a promising novel therapeutic target for Oral Squamous Cell Carcinoma.
Keywords:
AXLOSCCPROS1protein Ssquamous cell carcinoma

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