| First Author | McAndrews KM | Year | 2021 |
| Journal | Oncogene | Volume | 40 |
| Issue | 26 | Pages | 4440-4452 |
| PubMed ID | 34108617 | Mgi Jnum | J:307137 |
| Mgi Id | MGI:6718687 | Doi | 10.1038/s41388-021-01866-7 |
| Citation | McAndrews KM, et al. (2021) alphaSMA(+) fibroblasts suppress Lgr5(+) cancer stem cells and restrain colorectal cancer progression. Oncogene |
| abstractText | The development and progression of solid tumors is dependent on cancer cell autonomous drivers and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) in the TME possess both tumor-promoting and tumor-restraining functions. In the current study, we interrogated the role of alphaSMA(+) CAFs in a genetic mouse model of metastatic colorectal cancer (CRC). Selective depletion of alphaSMA(+) CAFs resulted in increased tumor invasiveness, lymph node metastasis, and reduced overall survival. Depletion of alphaSMA(+) CAFs reduced BMP4 and increased TGFbeta1 secretion from stromal cells, and was associated with increased Lgr5(+) cancer stem-like cells (CSCs) and the generation of an immunosuppressive TME with increased frequency of Foxp3(+) regulatory T cells and suppression of CD8(+) T cells. This study demonstrates that alphaSMA(+) CAFs in CRC exert tumor-restraining functions via BMP4/TGFbeta1 paracrine signaling that serves to suppress Lgr5(+) CSCs and promote anti-tumor immunity, ultimately limiting CRC progression. |
