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bioRxiv · 10.1101/2021.05.24.445438

Coordination of KIF3A and KIF13A regulates leading edge localization of MT1-MMP in cancer cells

Gifford, V.·Woskowicz, A. M.·Ito, N.·Balint, S.·Dustin, M.·Itoh, Y.
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Abstract

MT1-MMP plays a crucial role in promoting the cellular invasion of cancer cells by degrading the extracellular matrix to create a path for migration. During this process, its localization at the leading edge of migrating cells is critical, and it is achieved by targeted transport of MT1-MMP-containing vesicles along microtubules by kinesin superfamily proteins (KIFs). Here we identified three KIFs involved in MT1-MMP vesicle transport: KIF3A, KIF13A, and KIF9. Knockdown of KIF3A and KIF13A effectively inhibited MT1-MMP-dependent collagen degradation and invasion, while knockdown of KIF9 increased collagen degradation and invasion. Our data suggest that KIF9 competes with KIF3A/KIF13A to bring MT1-MMP vesicles to different locations in the plasma membrane. Live-cell imaging analyses have indicated that KIF3A and KIF13A coordinate to transport the same MT1-MMP-containing vesicles. Taken together, we have identified a unique interplay between three KIFs to regulate leading edge localization of MT1-MMP and MT1-MMP-dependent cancer cell invasion.

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Gifford, V., Woskowicz, A. M., Ito, N., Balint, S., Dustin, M., Itoh, Y.. 2021-05-24. Coordination of KIF3A and KIF13A regulates leading edge localization of MT1-MMP in cancer cells. https://doi.org/10.1101/2021.05.24.445438

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