Cargando…
Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant
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....
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718812/ https://www.ncbi.nlm.nih.gov/pubmed/31461652 http://dx.doi.org/10.1016/j.celrep.2019.07.092 |
_version_ | 1783447803044823040 |
---|---|
author | Bordignon, Pino Bottoni, Giulia Xu, Xiaoying Popescu, Alma S. Truan, Zinnia Guenova, Emmanuella Kofler, Lukas Jafari, Paris Ostano, Paola Röcken, Martin Neel, Victor Dotto, G. Paolo |
author_facet | Bordignon, Pino Bottoni, Giulia Xu, Xiaoying Popescu, Alma S. Truan, Zinnia Guenova, Emmanuella Kofler, Lukas Jafari, Paris Ostano, Paola Röcken, Martin Neel, Victor Dotto, G. Paolo |
author_sort | Bordignon, Pino |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6718812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67188122019-09-06 Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant Bordignon, Pino Bottoni, Giulia Xu, Xiaoying Popescu, Alma S. Truan, Zinnia Guenova, Emmanuella Kofler, Lukas Jafari, Paris Ostano, Paola Röcken, Martin Neel, Victor Dotto, G. Paolo Cell Rep Article 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. Cell Press 2019-08-27 /pmc/articles/PMC6718812/ /pubmed/31461652 http://dx.doi.org/10.1016/j.celrep.2019.07.092 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Bordignon, Pino Bottoni, Giulia Xu, Xiaoying Popescu, Alma S. Truan, Zinnia Guenova, Emmanuella Kofler, Lukas Jafari, Paris Ostano, Paola Röcken, Martin Neel, Victor Dotto, G. Paolo Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant |
title | Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant |
title_full | Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant |
title_fullStr | Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant |
title_full_unstemmed | Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant |
title_short | Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant |
title_sort | dualism of fgf and tgf-β signaling in heterogeneous cancer-associated fibroblast activation with etv1 as a critical determinant |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718812/ https://www.ncbi.nlm.nih.gov/pubmed/31461652 http://dx.doi.org/10.1016/j.celrep.2019.07.092 |
work_keys_str_mv | AT bordignonpino dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT bottonigiulia dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT xuxiaoying dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT popescualmas dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT truanzinnia dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT guenovaemmanuella dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT koflerlukas dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT jafariparis dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT ostanopaola dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT rockenmartin dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT neelvictor dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant AT dottogpaolo dualismoffgfandtgfbsignalinginheterogeneouscancerassociatedfibroblastactivationwithetv1asacriticaldeterminant |