Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.
Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.
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癌症相关成纤维细胞的信号通路和癌症靶向治疗
DOI：
10.1038/s41392-021-00641-0
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发表时间：
2021-06-10
影响因子：
39.3
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Wu F;Yang J;Liu J;Wang Y;Mu J;Zeng Q;Deng S;Zhou H
为了繁荣，癌症在很大程度上依赖于其周围的肿瘤微环境（TME），并且TME中的癌症相关成纤维细胞（CAF）对于癌症的发生和进展至关重要，因为它们在细胞外基质重塑、维持干性、血管形成、调节肿瘤代谢、免疫应答以及促进癌细胞增殖、迁移、侵袭和治疗抗性中具有多方面的作用。CAF是高度异质性的基质细胞，它们与癌细胞的相互作用由复杂且错综复杂的信号传导网络介导，所述信号传导网络由转化生长因子-β、磷酸肌醇3-激酶/AKT/雷帕霉素的哺乳动物靶标、促分裂原活化蛋白激酶、Wnt、Janus激酶/转录的信号转导子和活化子、表皮生长因子受体、Hippo和活化B细胞的核因子κ-轻链-增强子组成，等等，信号通路CAFs中的这些信号在癌症进展过程中表现出自己的特殊性，并有可能成为抗癌治疗的靶点。因此，全面了解癌细胞和CAFs之间相互作用中的这些信号级联对于充分认识CAFs在癌症中的关键作用是必要的。在此，我们将总结大量的研究结果，对信号介导的crosstalk的CAFs与癌细胞及其相关的目标或试验。此外，我们假设三种潜在的靶向策略，包括上皮-间充质共同靶点、顺序靶点扰动和串扰导向的信号转导靶点，为CAF导向或宿主细胞导向的抗肿瘤治疗铺平了道路。
To flourish, cancers greatly depend on their surrounding tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in TME are critical for cancer occurrence and progression because of their versatile roles in extracellular matrix remodeling, maintenance of stemness, blood vessel formation, modulation of tumor metabolism, immune response, and promotion of cancer cell proliferation, migration, invasion, and therapeutic resistance. CAFs are highly heterogeneous stromal cells and their crosstalk with cancer cells is mediated by a complex and intricate signaling network consisting of transforming growth factor-beta, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin, mitogen-activated protein kinase, Wnt, Janus kinase/signal transducers and activators of transcription, epidermal growth factor receptor, Hippo, and nuclear factor kappa-light-chain-enhancer of activated B cells, etc., signaling pathways. These signals in CAFs exhibit their own special characteristics during the cancer progression and have the potential to be targeted for anticancer therapy. Therefore, a comprehensive understanding of these signaling cascades in interactions between cancer cells and CAFs is necessary to fully realize the pivotal roles of CAFs in cancers. Herein, in this review, we will summarize the enormous amounts of findings on the signals mediating crosstalk of CAFs with cancer cells and its related targets or trials. Further, we hypothesize three potential targeting strategies, including, namely, epithelial–mesenchymal common targets, sequential target perturbation, and crosstalk-directed signaling targets, paving the way for CAF-directed or host cell-directed antitumor therapy.
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影响因子：
3.7
作者：
Bliss LA;Sams MR;Deep-Soboslay A;Ren-Patterson R;Jaffe AE;Chenoweth JG;Jaishankar A;Kleinman JE;Hyde TM
通讯作者：
Hyde TM
影响因子：
8
作者：
Aprelikova, O.;Palla, J.;Hibler, B.;Yu, X.;Greer, Y. E.;Yi, M.;Stephens, R.;Maxwell, G. L.;Jazaeri, A.;Risinger, J. I.;Rubin, J. S.;Niederhuber, J.
通讯作者：
Niederhuber, J.
影响因子：
7.4
作者：
Bonneau, Claire;Elies, Antoine;Mechta-Grigoriou, Fatima
通讯作者：
Mechta-Grigoriou, Fatima
影响因子：
16.6
作者：
Bao M;Xie J;Piruska A;Huck WTS
通讯作者：
Huck WTS
影响因子：
4.6
作者：
Bauer, Jessica;Emon, Md Abdul Bashar;Jung, Barbara
通讯作者：
Jung, Barbara