| First Author | Flanagan DJ | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 7551 |
| PubMed ID | 36477656 | Mgi Jnum | J:332124 |
| Mgi Id | MGI:7410206 | Doi | 10.1038/s41467-022-35134-3 |
| Citation | Flanagan DJ, et al. (2022) Epithelial TGFbeta engages growth-factor signalling to circumvent apoptosis and drive intestinal tumourigenesis with aggressive features. Nat Commun 13(1):7551 |
| abstractText | The pro-tumourigenic role of epithelial TGFbeta signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFbeta signalling. In the presence of concurrent Apc and Kras mutations, activation of epithelial TGFbeta signalling rampantly accelerates tumourigenesis and share transcriptional signatures with those of the born to be bad T1 human tumours and predicts recurrence in stage II CRC. Mechanistically, epithelial TGFbeta signalling induces a growth-promoting EGFR-signalling module that synergises with mutant APC and KRAS to drive MAPK signalling that re-sensitise tumour cells to MEK and/or EGFR inhibitors. Together, we identify epithelial TGFbeta signalling both as a determinant of early dissemination and a potential therapeutic vulnerability of CRC's with born to be bad traits. |
