Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives.
Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives.
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DOI：
10.1002/cac2.12392
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发表时间：
2023-01
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影响因子：
--
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作为肿瘤微环境（TME）的重要组成部分，癌症相关成纤维细胞（CAF）在癌症的发生和发展中起着重要作用。众所周知的信号通路，包括转化生长因子-β（TGF-β）、Hedgehog（Hh）、Notch、Wnt、Hippo、核因子κ-B（NF-κB）、Janus激酶（JAK）/信号转导和转录激活因子（STAT）、促分裂原活化蛋白激酶（MAPK）和磷酸肌醇3-激酶（PI 3 K）/AKT通路，以及转录因子，包括缺氧诱导因子（HIF）、热休克转录因子1（HSF 1）、P53、Snail和Twist构成TME中复杂的调节网络，以调节CAF的形成、活化、异质性、代谢特征和恶性表型。激活的CAFs通过改变转录和分泌特性来重塑TME并影响癌细胞的恶性生物学过程，这种调节部分依赖于信号级联的调节。临床前和临床试验的结果表明，靶向CAF中信号通路的疗法显示出有希望的疗效，但也伴随着一些失败（例如，NCT 01130142和NCT 01064622）。因此，全面了解CAF中的信号级联可能有助于我们更好地了解CAF和TME在癌症进展中的作用，并可能促进更有效和更安全的基质靶向癌症治疗的发展。本文就CAF信号通路的研究进展作一综述，并对CAF的研究前景作一展望。
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.
影响因子：
9
作者：
Sun Y;Yang D;Xi L;Chen Y;Fu L;Sun K;Yin J;Li X;Liu S;Qin Y;Liu M;Hou Y
通讯作者：
Hou Y