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PreprintCited by 8Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingCancer Cells and Metastasis

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

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Menin, Luca, Weber, Janine, Villa, Stefano, Martini, Emanuele, Maspero, Elena, Cancila, Valeria, Maiuri, Paolo, Palamidessi, Andrea, Frittoli, Emanuela, Bianchi, Fabrizio, Tripodo, Claudio, Walters, Kylie J., Giavazzi, Fabio, Scita, Giorgio, Polo, Simona·2023·Cell Reports
DOI 10.1101/2023.01.23.524898PMC PMC10530600

Preprint — published as 10.1016/j.celrep.2023.113001

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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. Highlights: Collective motion of jammed epithelia requires myosin VI activity The MYO6-DOCK7 axis is critical to restrict the activity of RAC1 in a planar polarized fashion MYO6-DOCK7-RAC1 activation ensures long-range coordination of movements by promoting orientation and persistence of cryptic lamellipodia Myosin VI overexpression is exploited by infiltrating breast cancer cells

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Metadata

Authors
Menin, L., Weber, J., Villa, S., Martini, E., Maspero, E., Cancila, V., Maiuri, P., Palamidessi, A., Frittoli, E., Bianchi, F., Tripodo, C., Walters, K. J., Giavazzi, F., Scita, G., & Polo, S.
Affiliations
  • IFOM (IT)
  • University of Milan (IT)
  • University of Palermo (IT)
  • University of Naples Federico II (IT)
  • Casa Sollievo della Sofferenza (IT)
  • National Institutes of Health (US)
Corresponding author
  • Scita, Giorgio
  • Polo, Simona
ORCID
Venue
Cell Reports
Publisher
openRxiv
Published
2023-01-23
Volume
42
Issue
8
Pages
113001-113001
ISSN
2211-1247 (ISSN-L)
DOI
10.1101/2023.01.23.524898
PMC
PMC10530600
OpenAlex
W4385879866
Cited by
8
References
1
Citations by year
2026: 3 · 2025: 4 · 2024: 1
FWCI
1.15
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, cc-by-nc-nd)
  • PubMed Central (submittedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • BOA (University of Milano-Bicocca) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Commission (101071470)
  • Associazione Italiana per la Ricerca sul Cancro (19875, #18621, 22759)
  • National Institutes of Health
  • National Cancer Institute (ZIABC011627)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
myosin VI, DOCK7, Rac1, collective cell migration, lamellipodia, mammary epithelium, metastasis

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