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

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 wit

SUBMITTER: Bordignon P 

PROVIDER: S-EPMC6718812 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature