Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant.

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State: Public
Version: author
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_450CF627543E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant.
Journal
Cell reports
Author(s)
Bordignon P., Bottoni G., Xu X., Popescu A.S., Truan Z., Guenova E., Kofler L., Jafari P., Ostano P., Röcken M., Neel V., Dotto G.P.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
27/08/2019
Peer-reviewed
Oui
Volume
28
Number
9
Pages
2358-2372.e6
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Heterogeneity of cancer-associated fibroblasts (CAFs) can result from activation of distinct signaling pathways. We show that in primary human dermal fibroblasts (HDFs), fibroblast growth factor (FGF) and transforming growth factor β (TGF-β) signaling oppositely modulate multiple CAF effector genes. Genetic abrogation or pharmacological inhibition of either pathway results in induction of genes responsive to the other, with the ETV1 transcription factor mediating the FGF effects. Duality of FGF/TGF-β signaling and differential ETV1 expression occur in multiple CAF strains and fibroblasts of desmoplastic versus non-desmoplastic skin squamous cell carcinomas (SCCs). Functionally, HDFs with opposite TGF-β versus FGF modulation converge on promoting cancer cell proliferation. However, HDFs with increased TGF-β signaling enhance invasive properties and epithelial-mesenchymal transition (EMT) of SCC cells, whereas HDFs with increased FGF signaling promote macrophage infiltration. The findings point to a duality of FGF versus TGF-β signaling in distinct CAF populations that promote cancer development through modulation of different processes.
Keywords
CAF, EMT, ETV1, FGF, SCC, TGF-β, cancer-associated fibroblasts, inflammation, macrophages, skin cancer
Pubmed
Web of science
Open Access
Yes
Create date
17/09/2019 15:30
Last modification date
15/07/2020 6:26
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