| First Author | Choi S | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10384 | PubMed ID | 26785948 |
| Mgi Jnum | J:235886 | Mgi Id | MGI:5803911 |
| Doi | 10.1038/ncomms10384 | Citation | Choi S, et al. (2016) Bcl-xL promotes metastasis independent of its anti-apoptotic activity. Nat Commun 7:10384 |
| abstractText | Bcl-xL suppresses mitochondria-mediated apoptosis and is frequently overexpressed in cancer to promote cancer cell survival. Bcl-xL also promotes metastasis. However, it is unclear whether this metastatic function is dependent on its anti-apoptotic activity in the mitochondria. Here we demonstrate that Bcl-xL promotes metastasis independent of its anti-apoptotic activity. We show that apoptosis-defective Bcl-xL mutants and an engineered Bcl-xL targeted to the nucleus promote epithelial-mesenchymal transition, migration, invasion and stemness in pancreatic neuroendocrine tumour (panNET) and breast cancer cell lines. However, Bcl-xL proteins targeted to the mitochondria or outside of the nucleus do not have these functions. We confirm our findings in spontaneous and xenograft mouse models. Furthermore, Bcl-xL exerts metastatic function through epigenetic modification of the TGFbeta promoter to increase TGFbeta signalling. Consistent with these findings, we detect nuclear Bcl-xL in human metastatic panNETs. Taken together, the metastatic function of Bcl-xL is independent of its anti-apoptotic activity and its residence in the mitochondria. |
