| First Author | Gudiño V | Year | 2021 |
| Journal | Cell Death Dis | Volume | 12 |
| Issue | 10 | Pages | 873 |
| PubMed ID | 34564693 | Mgi Jnum | J:312356 |
| Mgi Id | MGI:6784458 | Doi | 10.1038/s41419-021-04177-7 |
| Citation | Gudino V, et al. (2021) Negative regulation of TGFbeta-induced apoptosis by RAC1B enhances intestinal tumourigenesis. Cell Death Dis 12(10):873 |
| abstractText | RAC1B is a tumour-related alternative splice isoform of the small GTPase RAC1, found overexpressed in a large number of tumour types. Building evidence suggests it promotes tumour progression but compelling in vivo evidence, demonstrating a role in driving tumour invasion, is currently lacking. In the present study, we have overexpressed RAC1B in a colorectal cancer mouse model with potential invasive properties. Interestingly, RAC1B overexpression did not trigger tumour invasion, rather it led to an acceleration of tumour initiation and reduced mouse survival. By modelling early stages of adenoma initiation we observed a reduced apoptotic rate in RAC1B overexpressing tumours, suggesting protection from apoptosis as a mediator of this phenotype. RAC1B overexpressing tumours displayed attenuated TGFbeta signalling and functional analysis in ex vivo organoid cultures demonstrated that RAC1B negatively modulates TGFbeta signalling and confers resistance to TGFbeta-driven cell death. This work defines a novel mechanism by which early adenoma cells can overcome the cytostatic and cytotoxic effects of TGFbeta signalling and characterises a new oncogenic function of RAC1B in vivo. |
