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

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. M...

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Published in:European journal of cell biology 2022-01, Vol.101 (1), p.151197-151197, Article 151197
Main Authors: Abdellatef, Sandra, Fakhoury, Isabelle, Haddad, Maria Al, Jaafar, Leila, Maalouf, Hiba, Hanna, Samer, Khalil, Bassem, El Masri, Zeinab, Hodgson, Louis, El-Sibai, Mirvat
Format: Article
Language:English
Subjects:
Adenocarcinoma
Cdc42
cdc42 GTP-Binding Protein - genetics
Cell invasion
Cell Line, Tumor
GTPase-Activating Proteins - genetics
Humans
Invadopodia
Neoplasm Invasiveness
Ovarian cancer
Podosomes
StarD13
Tumor Suppressor Proteins - genetics
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Summary: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. •StarD13 depletion does not affect the 2D motility of ovarian cancer cells.•StarD13 inhibits ovarian cancer cell invasion through the inhibition of Cdc42.•StarD13 does not localize to mature TKS4-labeled invadopodia that possess matrix degradation ability, while Cdc42 does.•StarD13 localization and Cdc42 activation appear mutually exclusive in invadopodial structures.•Cdc42 might directly recruit TKS4 to invadopodia.
ISSN:0171-9335
1618-1298
DOI:10.1016/j.ejcb.2021.151197