TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia
TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia
Abstract During breast cancer metastasis, cancer cell invasion is driven by actin-rich protrusions called invadopodia, which mediate the extracellular matrix degradation required for the success of the invasive cascade. In this study, we demonstrated that TC10, a member of a Cdc42 subfamily of p21 small GTPases, regulates the membrane type 1 matrix metalloproteinase (MT1-MMP)-driven extracellular matrix degradation at invadopodia. We show that TC10 is required for the plasma membrane surface exposure of MT1-MMP at invadopodia. By utilizing our new F?rster resonance energy transfer (FRET) biosensor, we demonstrated the p190RhoGAP-dependent regulation of spatiotemporal TC10 activity at invadopodia. We identified a pathway that regulates TC10 activity and function at invadopodia through the activation of p190RhoGAP and the downstream interacting effector Exo70 at the invadopodia sites. Our findings reveal the role of a previously unknown regulator of vesicular fusion at invadopodia, TC10, on the invasive potential of breast cancer cells during invasion and metastasis.
H¨1lsemann M.、Segall J.E.、Mao S.P.H.、Verkhusha P.V.、Hodgson L.、Donnelly S.K.
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine||Gruss-Lipper Biophotonics Center, Albert Einstein College of MedicineDepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine||Gruss-Lipper Biophotonics Center, Albert Einstein College of MedicineDepartment of Anatomy and Structural Biology, Albert Einstein College of MedicineDepartment of Anatomy and Structural Biology, Albert Einstein College of MedicineDepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine||Gruss-Lipper Biophotonics Center, Albert Einstein College of MedicineDepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine
肿瘤学细胞生物学分子生物学
H¨1lsemann M.,Segall J.E.,Mao S.P.H.,Verkhusha P.V.,Hodgson L.,Donnelly S.K..TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/2020.11.17.386854.点此复制
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