成纤维细胞生长因子
转化生长因子
细胞生物学
信号转导
生物
癌症研究
上皮-间质转换
转录因子
癌细胞
成纤维细胞
转化生长因子β
效应器
癌症
细胞培养
遗传学
基因
受体
转移
作者
Pino Bordignon,Giulia Bottoni,Xiaoying Xu,Alma S. Popescu,Zinnia Truan,Emmanuella Guenova,Lukas Kofler,Paris Jafari,Paola Ostano,Martin Röcken,Victor Neel,G. Paolo Dotto
出处
期刊:Cell Reports
[Elsevier]
日期:2019-08-01
卷期号:28 (9): 2358-2372.e6
被引量:72
标识
DOI:10.1016/j.celrep.2019.07.092
摘要
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.
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