StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42 |
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| Affiliation: | 1. Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon;2. Department of Pediatrics Hematology/Oncology division, Weill Cornell Medicine, Joan & Sanford I. Weill Medical College of Cornell University, Ithaca, NY, USA;3. Department of Medicine, Icahn School of Medicine at Mount Sinai, Department of Biological Sciences, Fordham University, Bronx, NY, USA;4. Department of Biochemistry and Molecular Biology, University Park, Pennsylvania State University, State College, PA, USA;5. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA;6. Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA |
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| 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. |
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| Keywords: | StarD13 Ovarian cancer Cell invasion Invadopodia Cdc42 |
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