Regulation and functional significance of CDC42 alternative splicing in ovarian cancer

Xiaolong He1, Chengfu Yuan2, Jilai Yang1

  • 1Department of Biopharmaceutical Sciences, College of Pharmacy-Rockford, The University of Illinois at Chicago, Rockford, IL 61107, USA.

Oncotarget
|September 5, 2015
PubMed

Insights

The splicing factor PTBP1 influences tumorigenesis by regulating CDC42 alternative splicing. A specific variant, CDC42-v2, suppresses ovarian tumor growth and may act as a tumor suppressor.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The splicing factor polypyrimidine tract-binding protein 1 (PTBP1) is implicated in tumorigenesis, but its precise mechanism is not fully understood.
  • Filopodia formation is crucial for cell motility and invasion in cancer, regulated by proteins like CDC42.

Purpose of the Study:

  • To elucidate the mechanism by which PTBP1 contributes to tumorigenesis.
  • To investigate the role of PTBP1 in regulating filopodia formation through CDC42 alternative splicing.

Main Methods:

  • Knockdown of PTBP1 in cancer cells.
  • Analysis of CDC42 alternative splicing variants (CDC42-v1 and CDC42-v2).
  • Quantitative RT-PCR to assess variant expression in cell lines and tumor tissues.
  • Functional assays including filopodia formation, cell growth, soft agar colony formation, and invasiveness assays.

Main Results:

  • PTBP1 knockdown inhibited filopodia formation.
  • PTBP1 regulates alternative splicing of CDC42, increasing the expression of CDC42-v2.
  • CDC42-v2 suppressed filopodia formation, cell growth, colony formation, and invasiveness, unlike CDC42-v1.
  • CDC42-v2 expression was lower in ovarian cancer cells and tissues compared to normal controls.

Conclusions:

  • PTBP1's role in tumorigenesis is partly mediated by its regulation of CDC42 alternative splicing.
  • CDC42-v2 functions as a tumor suppressor by inhibiting ovarian tumor cell growth, colony formation, and invasiveness.
  • Targeting PTBP1 or modulating CDC42-v2 levels may offer therapeutic strategies for ovarian cancer.

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