Biology subjects

Palamidessi, A.

Publications and source records attributed to Palamidessi, A..

2 recordsLinked to original sources

bioRxiv2023

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

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

cell biology↗

bioRxiv2018

Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma.

During wound repair, branching morphogenesis and carcinoma dissemination, cellular rearrangements are fostered by a solid-to-liquid transition known as unjamming. The biomolecular machinery behind unjamming, its physiological and clinical relevance remain, however, a mystery. Here, we combine biophysical and biochemical analysis to study unjamming in a variety of epithelial 2D and 3D collectives: monolayers, differentiated normal mammary cysts, spheroid models of breast ductal carcinoma in situ (DCIS), and ex vivo slices of orthotopically-implanted DCIS. In all cases, elevation of the small GTPase RAB5A sparks unjamming by promoting non-clathrin-dependent internalization of epidermal growth factor receptor that leads to hyper-activation of endosomally-confined ERK1/2 and phosphorylation of the actin nucleator WAVE2. Physically, activation of this pathway causes highly coordinated flocking of the cells, with striking rotational motion in 3D that eventually leads to matrix remodelling and collective invasiveness of otherwise jammed carcinoma. The identified endo-ERK1/2 pathway provides an effective switch for unjamming through flocking to promote epithelial tissues morphogenesis and carcinoma invasion and dissemination.

cancer biology↗