Homeostatic membrane tension constrains cancer cell dissemination by counteracting BAR protein assembly.
Biomechanical Phenomena
Cell Line, Tumor
Cell Membrane
/ chemistry
Cell Movement
DNA-Binding Proteins
/ genetics
Epithelial Cells
/ metabolism
Epithelial-Mesenchymal Transition
/ genetics
Gene Expression Regulation, Neoplastic
Homeostasis
/ genetics
Humans
Lymphatic Metastasis
Mechanotransduction, Cellular
/ genetics
Neoplasm Invasiveness
Optical Tweezers
Protein Serine-Threonine Kinases
/ genetics
Surface Tension
Transcription Factors
/ genetics
rhoA GTP-Binding Protein
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 10 2021
11 10 2021
Historique:
received:
02
03
2020
accepted:
16
09
2021
entrez:
12
10
2021
pubmed:
13
10
2021
medline:
4
11
2021
Statut:
epublish
Résumé
Malignancy is associated with changes in cell mechanics that contribute to extensive cell deformation required for metastatic dissemination. We hypothesized that the cell-intrinsic physical factors that maintain epithelial cell mechanics could function as tumor suppressors. Here we show, using optical tweezers, genetic interference, mechanical perturbations, and in vivo studies, that epithelial cells maintain higher plasma membrane (PM) tension than their metastatic counterparts and that high PM tension potently inhibits cancer cell migration and invasion by counteracting membrane curvature sensing/generating BAR family proteins. This tensional homeostasis is achieved by membrane-to-cortex attachment (MCA) regulated by ERM proteins, whose disruption spontaneously transforms epithelial cells into a mesenchymal migratory phenotype powered by BAR proteins. Consistently, the forced expression of epithelial-mesenchymal transition (EMT)-inducing transcription factors results in decreased PM tension. In metastatic cells, increasing PM tension by manipulating MCA is sufficient to suppress both mesenchymal and amoeboid 3D migration, tumor invasion, and metastasis by compromising membrane-mediated mechanosignaling by BAR proteins, thereby uncovering a previously undescribed mechanical tumor suppressor mechanism.
Identifiants
pubmed: 34635648
doi: 10.1038/s41467-021-26156-4
pii: 10.1038/s41467-021-26156-4
pmc: PMC8505629
doi:
Substances chimiques
DNA-Binding Proteins
0
ETV5 protein, human
0
Transcription Factors
0
RHOA protein, human
124671-05-2
SLK protein, human
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
rhoA GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5930Informations de copyright
© 2021. The Author(s).
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