生物
间充质干细胞
间质细胞
细胞生物学
细胞分化
癌症研究
肿瘤微环境
表型
干细胞
肿瘤进展
肌成纤维细胞
免疫学
作者
Linda L. Tran,Truong D. Dang,Rintu Thomas,David R. Rowley
出处
期刊:Stem Cells
[Wiley]
日期:2021-12-01
卷期号:39 (12): 1766-1777
被引量:1
摘要
Stromal cells in the tumor microenvironment regulate the immune landscape and tumor progression. Yet, the ontogeny and heterogeneity of reactive stromal cells within tumors is not well understood. Carcinoma-associated fibroblasts exhibiting an inflammatory phenotype (iCAFs) have been identified within multiple cancers; however, mechanisms that lead to their recruitment and differentiation also remain undefined. Targeting these mechanisms therapeutically may be important in managing cancer progression. Here, we identify the ELF3 transcription factor as the canonical mediator of IL-1α-induced differentiation of prostate mesenchymal stem cells to an iCAF phenotype, typical of the tumor microenvironment. Furthermore, IL-1α-induced iCAFs were subsequently refractive to TGF-β1 induced trans-differentiation to a myofibroblast phenotype (myCAF), another key carcinoma-associated fibroblast subtype typical of reactive stroma in cancer. Restricted trans-differentiation was associated with phosphorylation of the YAP protein, indicating that interplay between ELF3 action and activation of the Hippo pathway are critical for restricting trans-differentiation of iCAFs. Together, these data show that the IL-1α/ELF3/YAP pathways are coordinate for regulating inflammatory carcinoma-associated fibroblast differentiation.
科研通智能强力驱动
Strongly Powered by AbleSci AI