Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer
Abstract 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 vesse...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-06-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-021-00641-0 |
| _version_ | 1818864919099998208 |
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| author | Fanglong Wu Jin Yang Junjiang Liu Ye Wang Jingtian Mu Qingxiang Zeng Shuzhi Deng Hongmei Zhou |
| author_facet | Fanglong Wu Jin Yang Junjiang Liu Ye Wang Jingtian Mu Qingxiang Zeng Shuzhi Deng Hongmei Zhou |
| author_sort | Fanglong Wu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-19T10:39:18Z |
| format | Article |
| id | doaj.art-2eaa011281254c5aa022f2132f41abd8 |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-12-19T10:39:18Z |
| publishDate | 2021-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-2eaa011281254c5aa022f2132f41abd82022-12-21T20:25:30ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352021-06-016113510.1038/s41392-021-00641-0Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancerFanglong Wu0Jin Yang1Junjiang Liu2Ye Wang3Jingtian Mu4Qingxiang Zeng5Shuzhi Deng6Hongmei Zhou7State Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityState Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityAbstract 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.https://doi.org/10.1038/s41392-021-00641-0 |
| spellingShingle | Fanglong Wu Jin Yang Junjiang Liu Ye Wang Jingtian Mu Qingxiang Zeng Shuzhi Deng Hongmei Zhou Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer Signal Transduction and Targeted Therapy |
| title | Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer |
| title_full | Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer |
| title_fullStr | Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer |
| title_full_unstemmed | Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer |
| title_short | Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer |
| title_sort | signaling pathways in cancer associated fibroblasts and targeted therapy for cancer |
| url | https://doi.org/10.1038/s41392-021-00641-0 |
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