StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42

Sandra Abdellatef, Isabelle Fakhoury, Maria Al Haddad, Leila Jaafar, Hiba Maalouf, Samer Hanna, Bassem Khalil, Zeinab El Masri, Louis Hodgson, Mirvat El-Sibai

Research output: Contribution to journalReview articlepeer-review

Abstract

Metastasis remains the main challenge to overcome for treating ovarian cancers. In this study, we investigate the potential role of the Cdc42 GAP StarD13 in the modulation of cell motility, invasion in ovarian cancer cells. StarD13 depletion does not affect the 2D motility of ovarian cancer cells. More importantly, StarD13 inhibits matrix degradation, invadopodia formation and cell invasion through the inhibition of Cdc42. StarD13 does not localize to mature TKS4-labeled invadopodia that possess matrix degradation ability, while a Cdc42 FRET biosensor, detects Cdc42 activation in these invadopodia. In fact, StarD13 localization and Cdc42 activation appear mutually exclusive in invadopodial structures. Finally, for the first time we uncover a potential role of Cdc42 in the direct recruitment of TKS4 to invadopodia. This study emphasizes the specific role of StarD13 as a narrow spatial regulator of Cdc42, inhibiting invasion, suggesting the suitability of StarD13 for targeted therapy.

Original languageEnglish (US)
Article number151197
JournalEuropean Journal of Cell Biology
Volume101
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • Cdc42
  • Cell invasion
  • Invadopodia
  • Ovarian cancer
  • StarD13

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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