RT Journal Article
SR Electronic
T1 TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.17.386854
DO 10.1101/2020.11.17.386854
A1 M. Hülsemann
A1 S.K. Donnelly
A1 P.V. Verkhusha
A1 S.P.H. Mao
A1 J.E. Segall
A1 L. Hodgson
YR 2020
UL http://biorxiv.org/content/early/2020/11/17/2020.11.17.386854.abstract
AB 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 Förster 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.Competing Interest StatementThe authors have declared no competing interest.