A planar polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia
Luca Menin,
Janine Weber,
Stefano Villa,
Emanuele Martini,
Elena Maspero,
Carlos A. Niño,
Valeria Cancila,
Alessandro Poli,
Paolo Maiuri,
Andrea Palamidessi,
Emanuela Frittoli,
Fabrizio Bianchi,
Claudio Tripodo,
Kylie J. Walters,
Fabio Giavazzi,
Giorgio Scita,
Simona Polo
Affiliations
Luca Menin
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy
Janine Weber
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy
Stefano Villa
Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Segrate, Italy
Emanuele Martini
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy
Elena Maspero
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy
Carlos A. Niño
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy
Valeria Cancila
Human Pathology Section, Department of Health Sciences, University of Palermo School of Medicine, Palermo, Italy
Alessandro Poli
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy
Paolo Maiuri
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy
Andrea Palamidessi
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy
Emanuela Frittoli
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy
Fabrizio Bianchi
Unit of Cancer Biomarkers, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
Claudio Tripodo
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy; Human Pathology Section, Department of Health Sciences, University of Palermo School of Medicine, Palermo, Italy
Kylie J. Walters
Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA
Fabio Giavazzi
Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Segrate, Italy
Giorgio Scita
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy; Dipartimento di Oncologia ed Emato-oncologia, Università degli Studi di Milano, Milan, Italy; Corresponding author
Simona Polo
IFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy; Dipartimento di Oncologia ed Emato-oncologia, Università degli Studi di Milano, Milan, Italy; Corresponding author
Summary: 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 lamellipodium 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 MYO6-DOCK7 axis essential for spatially restricting 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.
