PUBLICATION

Physical confinement promotes mesenchymal trans-differentiation of invading transformed cells in vivo

Authors
Zulueta-Coarasa, T., Fadul, J., Ahmed, M., Rosenblatt, J.
ID
ZDB-PUB-221104-3
Date
2022
Source
iScience   25: 105330 (Journal)
Registered Authors
Keywords
Cancer, Cell biology, Organizational aspects of cell biology
MeSH Terms
none
PubMed
36325066 Full text @ iScience
Abstract
Metastasis is tightly linked with poor cancer prognosis, yet it is not clear how transformed cells become invasive carcinomas. We previously discovered that single KRasV12-transformed cells can invade directly from the epithelium by basal cell extrusion. During this process, cells de-differentiate by mechanically pinching off their epithelial determinants, but how they trans-differentiate into a migratory, mesenchymal phenotype is not known. Here, we demonstrate that basally extruded KRasV12-expressing cells become significantly deformed as they invade the zebrafish body. Decreasing the confinement that cells experience after they invade reduces the percentage of KRasV12 cells that trans-differentiate into mesenchymal cell types, while higher confinement increases this percentage. Additionally, increased confinement promotes accumulation of internal masses over time. Altogether, our results suggest that mechanical forces drive not only de-differentiation of KRasV12-transformed epithelial cells as they invade but also their re-differentiation into mesenchymal phenotypes that contribute to distant metastases.
Genes / Markers
Marker Marker Type Name
lamc1GENElaminin, gamma 1
tp53GENEtumor protein p53
1 - 2 of 2
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Expression
Phenotype
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
e119TgTransgenic Insertion
    sa379
      		Point Mutation
      vu119TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        lamc1MO3-lamc1MRPHLNO
        tp53MO4-tp53MRPHLNO
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        Fish
        No data available
        Antibodies
        Orthology
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        mCherryEFGmCherry
        1 - 2 of 2
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        Mapping
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        Citation
        Zulueta-Coarasa, T., Fadul, J., Ahmed, M., Rosenblatt, J. (2022) Physical confinement promotes mesenchymal trans-differentiation of invading transformed cells in vivo. iScience. 25:105330.