Migration through physical constraints is enabled by MAPK-induced cell softening via actin cytoskeleton re-organization.
Actin Cytoskeleton
/ physiology
Anisotropy
Biomechanical Phenomena
/ physiology
Cell Line, Tumor
Cell Movement
/ physiology
Cell Plasticity
/ physiology
Cell Proliferation
Focal Adhesions
/ physiology
Humans
MAP Kinase Signaling System
/ physiology
Melanoma
/ physiopathology
Micropore Filters
Neoplasm Invasiveness
/ pathology
Neoplasm Metastasis
/ pathology
Proto-Oncogene Proteins B-raf
/ metabolism
Proto-Oncogene Proteins p21(ras)
/ metabolism
Cytoskeleton
Elasticity
MAPK
Motility
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
31 05 2019
31 05 2019
Historique:
received:
20
08
2018
accepted:
25
04
2019
entrez:
2
6
2019
pubmed:
4
6
2019
medline:
1
7
2020
Statut:
epublish
Résumé
Cancer cells are softer than the normal cells, and metastatic cells are even softer. These changes in biomechanical properties contribute to cancer progression by facilitating cell movement through physically constraining environments. To identify properties that enabled passage through physical constraints, cells that were more efficient at moving through narrow membrane micropores were selected from established cell lines. By examining micropore-selected human MDA MB 231 breast cancer and MDA MB 435 melanoma cancer cells, membrane fluidity and nuclear elasticity were excluded as primary contributors. Instead, reduced actin cytoskeleton anisotropy, focal adhesion density and cell stiffness were characteristics associated with efficient passage through constraints. By comparing transcriptomic profiles between the parental and selected populations, increased Ras/MAPK signalling was linked with cytoskeleton rearrangements and cell softening. MEK inhibitor treatment reversed the transcriptional, cytoskeleton, focal adhesion and elasticity changes. Conversely, expression of oncogenic KRas in parental MDA MB 231 cells, or oncogenic BRaf in parental MDA MB 435 cells, significantly reduced cell stiffness. These results reveal that MAPK signalling, in addition to tumour cell proliferation, has a significant role in regulating cell biomechanics.This article has an associated First Person interview with the first author of the paper.
Identifiants
pubmed: 31152052
pii: 132/11/jcs224071
doi: 10.1242/jcs.224071
pmc: PMC6589089
pii:
doi:
Substances chimiques
KRAS protein, human
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
ID : A18276
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M018776/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A17196
Pays : United Kingdom
Informations de copyright
© 2019. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
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