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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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Autores principales: Abdellatef, Sandra, Fakhoury, Isabelle, Al Haddad, Maria, Jaafar, Leila, Maalouf, Hiba, Hanna, Samer, Khalil, Bassem, El Masri, Zeinab, Hodgson, Louis, El-Sibai, Mirvat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756770/
https://www.ncbi.nlm.nih.gov/pubmed/34958986
http://dx.doi.org/10.1016/j.ejcb.2021.151197
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author Abdellatef, Sandra
Fakhoury, Isabelle
Al Haddad, Maria
Jaafar, Leila
Maalouf, Hiba
Hanna, Samer
Khalil, Bassem
El Masri, Zeinab
Hodgson, Louis
El-Sibai, Mirvat
author_facet Abdellatef, Sandra
Fakhoury, Isabelle
Al Haddad, Maria
Jaafar, Leila
Maalouf, Hiba
Hanna, Samer
Khalil, Bassem
El Masri, Zeinab
Hodgson, Louis
El-Sibai, Mirvat
author_sort Abdellatef, Sandra
collection PubMed
description 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.
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spelling pubmed-87567702023-01-01 StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42 Abdellatef, Sandra Fakhoury, Isabelle Al Haddad, Maria Jaafar, Leila Maalouf, Hiba Hanna, Samer Khalil, Bassem El Masri, Zeinab Hodgson, Louis El-Sibai, Mirvat Eur J Cell Biol Article 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. 2022-01 2021-12-21 /pmc/articles/PMC8756770/ /pubmed/34958986 http://dx.doi.org/10.1016/j.ejcb.2021.151197 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Abdellatef, Sandra
Fakhoury, Isabelle
Al Haddad, Maria
Jaafar, Leila
Maalouf, Hiba
Hanna, Samer
Khalil, Bassem
El Masri, Zeinab
Hodgson, Louis
El-Sibai, Mirvat
StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42
title StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42
title_full StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42
title_fullStr StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42
title_full_unstemmed StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42
title_short StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42
title_sort stard13 negatively regulates invadopodia formation and invasion in high-grade serous (hgs) ovarian adenocarcinoma cells by inhibiting cdc42
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756770/
https://www.ncbi.nlm.nih.gov/pubmed/34958986
http://dx.doi.org/10.1016/j.ejcb.2021.151197
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