Publications Repository

Publications Repository

View Item 
  •   Home
  • ICR Divisions
  • Closed Research Teams
  • View Item
  • Home
  • ICR Divisions
  • Closed Research Teams
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization.

Thumbnail
View/Open
Published version (16.93Mb)
Publication Date
2015-12-06
ICR Author
Calvo, Fernando
Author
Del Pozo Martin, Y
Park, D
Ramachandran, A
Ombrato, L
Calvo, F
Chakravarty, P
Spencer-Dene, B
Derzsi, S
Hill, CS
Sahai, E
Malanchi, I
Type
Journal Article
Metadata
Show full item record
Abstract
During metastatic colonization, tumor cells must establish a favorable microenvironment or niche that will sustain their growth. However, both the temporal and molecular details of this process remain poorly understood. Here, we found that metastatic initiating cells (MICs) exhibit a high capacity for lung fibroblast activation as a result of Thrombospondin 2 (THBS2) expression. Importantly, inhibiting the mesenchymal phenotype of MICs by blocking the epithelial-to-mesenchymal transition (EMT)-associated kinase AXL reduces THBS2 secretion, niche-activating ability, and, consequently, metastatic competence. Subsequently, disseminated metastatic cells revert to an AXL-negative, more epithelial phenotype to proliferate and decrease the phosphorylation levels of TGF-β-dependent SMAD2-3 in favor of BMP/SMAD1-5 signaling. Remarkably, newly activated fibroblasts promote this transition. In summary, our data reveal a crosstalk between cancer cells and their microenvironment whereby the EMT status initially triggers and then is regulated by niche activation during metastatic colonization.
URL
https://repository.icr.ac.uk/handle/internal/327
Collections
  • Closed Research Teams
Licenseref URL
https://creativecommons.org/licenses/by-nc-nd/4.0
Version of record
10.1016/j.celrep.2015.11.025
Subject
Cell Line, Tumor
Animals
Mice, Transgenic
Humans
Mice
Mice, Nude
Breast Neoplasms
Lung Neoplasms
Neoplasm Metastasis
Disease Models, Animal
Triazoles
Benzocycloheptenes
Receptor Protein-Tyrosine Kinases
Transforming Growth Factor beta
Homeodomain Proteins
Thrombospondins
Proto-Oncogene Proteins
Transplantation, Heterologous
Signal Transduction
Cell Survival
RNA Interference
Female
Smad Proteins
Neoplastic Stem Cells
Epithelial-Mesenchymal Transition
CD24 Antigen
Research team
Tumour Microenvironment
Language
eng
Date accepted
2015-11-04
License start date
2015-12-06
Citation
Cell reports, 2015, 13 (11), pp. 2456 - 2469

Browse

All of ICR repositoryICR DivisionsIssue dateAuthorsTitlesSubjectsThis collectionIssue dateAuthorsTitlesSubjects

Statistics

Most popular itemsStatistics by countryMost popular authors
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.