Academic Journal
Cancer-associated Fibroblasts Promote Irradiated Cancer Cell Recovery Through Autophagy
| Title: | Cancer-associated Fibroblasts Promote Irradiated Cancer Cell Recovery Through Autophagy |
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| Authors: | Yongbin Wang, Guifang Gan, Bocheng Wang, Jinliang Wu, Yuan Cao, Dan Zhu, Yan Xu, Xiaona Wang, Hongxiu Han, Xiaoling Li, Ming Ye, Jiangmin Zhao, Jun Mi |
| Source: | EBioMedicine, Vol 17, Iss C, Pp 45-56 (2017) |
| Publisher Information: | Elsevier, 2017. |
| Publication Year: | 2017 |
| Collection: | LCC:Medicine LCC:Medicine (General) |
| Subject Terms: | Cancer-associated fibroblast, Cytokines, Intermediate metabolite, Autophagy, Tumor relapse, Radiation therapy, Medicine, Medicine (General), R5-920 |
| More Details: | Tumor relapse after radiotherapy is a significant challenge to oncologists, even after recent the advances in technologies. Here, we showed that cancer-associated fibroblasts (CAFs), a major component of cancer stromal cells, promoted irradiated cancer cell recovery and tumor relapse after radiotherapy. We provided evidence that CAFs-produced IGF1/2, CXCL12 and β-hydroxybutyrate were capable of inducing autophagy in cancer cells post-radiation and promoting cancer cell recovery from radiation-induced damage in vitro and in vivo in mice. These CAF-derived molecules increased the level of reactive oxygen species (ROS) post-radiation, which enhanced PP2A activity, repressing mTOR activation and increasing autophagy in cancer cells. Consistently, the IGF2 neutralizing antibody and the autophagy inhibitor 3-MA reduce the CAF-promoted tumor relapse in mice after radiotherapy. Taken together, our findings demonstrated that CAFs promoted irradiated cancer cell recovery and tumor regrowth post-radiation, suggesting that targeting the autophagy pathway in tumor cells may be a promising therapeutic strategy for radiotherapy sensitization. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2352-3964 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2352396417300786; https://doaj.org/toc/2352-3964 |
| DOI: | 10.1016/j.ebiom.2017.02.019 |
| Access URL: | https://doaj.org/article/a87889a651fe4233a99b2964db4c4087 |
| Accession Number: | edsdoj.87889a651fe4233a99b2964db4c4087 |
| Database: | Directory of Open Access Journals |
| ISSN: | 23523964 |
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| DOI: | 10.1016/j.ebiom.2017.02.019 |
| Published in: | EBioMedicine |
| Language: | English |