A planar-polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia

Menin, L.; Weber, J.; Villa, S.; Martini, E.; Maspero, E.; Cancila, V.; Maiuri, P.; Palamidessi, A.; Frittoli, E.; Bianchi, F.; Tripodo, C.; Walters, K.; Giavazzi, F.; Scita, G.; Polo, S.

doi:10.1101/2023.01.23.524898

bioRxiv · 10.1101/2023.01.23.524898

A planar-polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia

Menin, L.·Weber, J.·Villa, S.·Martini, E.·Maspero, E.·Cancila, V.·Maiuri, P.·Palamidessi, A.·Frittoli, E.·Bianchi, F.·Tripodo, C.·Walters, K.·Giavazzi, F.·Scita, G.·Polo, S.

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Abstract

Tissue fluidification and collective motility are pivotal in regulating embryonic morphogenesis, wound healing and tumor metastasis. These processes frequently require that each cell constituent of a tissue coordinates its migration activity and directed motion through the oriented extension of lamellipodia cell protrusions, promoted by RAC1 activity. While the upstream RAC1 regulators in individual migratory cells or leader cells during invasion or wound healing are well characterized, how RAC1 is controlled in follower cells remains unknown. Here, we identify a novel MYO6-DOCK7 axis that is critical for spatially restriction of RAC1 activity in a planar polarized fashion in model tissue monolayers. The MYO6-DOCK7 axis specifically controls the extension of cryptic lamellipodia required to drive tissue fluidification and cooperative mode motion in otherwise solid and static carcinoma cell collectives. HighlightsO_LICollective motion of jammed epithelia requires myosin VI activity C_LIO_LIThe MYO6-DOCK7 axis is critical to restrict the activity of RAC1 in a planar polarized fashion C_LIO_LIMYO6-DOCK7-RAC1 activation ensures long-range coordination of movements by promoting orientation and persistence of cryptic lamellipodia C_LIO_LIMyosin VI overexpression is exploited by infiltrating breast cancer cells C_LI

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Menin, L., Weber, J., Villa, S., Martini, E., Maspero, E., Cancila, V., Maiuri, P., Palamidessi, A., Frittoli, E., Bianchi, F., Tripodo, C., Walters, K., Giavazzi, F., Scita, G., Polo, S.. 2023-01-23. A planar-polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia. https://doi.org/10.1101/2023.01.23.524898

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