Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives

Cancer Communications

article

Zengli Fang¹  Qingcai Meng¹  Jin Xu¹  Wei Wang¹  Bo Zhang¹  Jiang Liu¹  Chen Liang¹  Jie Hua¹  Yingjun Zhao²  Xianjun Yu¹  Si Shi¹ 

[1] Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center;Department of Oncology, Shanghai Medical College, Fudan University;Shanghai Pancreatic Cancer Institute;Pancreatic Cancer Institute, Fudan University;Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University

关键词: Signaling pathways;    Cancer-associated fibroblasts;    Cell-cell interaction;    Tumor microenvironment;    Therapeutic targets;   

DOI  :  10.1002/cac2.12392

学科分类：社会科学、人文和艺术（综合）

来源: Springer

【 摘 要 】

As a critical component of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) play important roles in cancer initiation and progression. Well-known signaling pathways, including the transforming growth factor-β (TGF-β), Hedgehog (Hh), Notch, Wnt, Hippo, nuclear factor kappa-B (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)/AKT pathways, as well as transcription factors, including hypoxia-inducible factor (HIF), heat shock transcription factor 1 (HSF1), P53, Snail, and Twist, constitute complex regulatory networks in the TME to modulate the formation, activation, heterogeneity, metabolic characteristics and malignant phenotype of CAFs. Activated CAFs remodel the TME and influence the malignant biological processes of cancer cells by altering the transcriptional and secretory characteristics, and this modulation partially depends on the regulation of signaling cascades. The results of preclinical and clinical trials indicated that therapies targeting signaling pathways in CAFs demonstrated promising efficacy but were also accompanied by some failures (e.g., NCT01130142 and NCT01064622). Hence, a comprehensive understanding of the signaling cascades in CAFs might help us better understand the roles of CAFs and the TME in cancer progression and may facilitate the development of more efficient and safer stroma-targeted cancer therapies. Here, we review recent advances in studies of signaling pathways in CAFs and briefly discuss some future perspectives on CAF research.

【 授权许可】

CC BY|CC BY-NC-ND