Bcl-xL promotes metastasis independent of its anti-apoptotic activity Journal Article

Authors: Choi, S.; Chen, Z.; Tang, L. H.; Fang, Y.; Shin, S. J.; Panarelli, N. C.; Chen, Y. T.; Li, Y.; Jiang, X.; Du, Y. C. N.
Article Title: Bcl-xL promotes metastasis independent of its anti-apoptotic activity
Abstract: 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 TGFβ promoter to increase TGFβ 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.
Journal Title: Nature Communications
Volume: 7
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2016-01-20
Start Page: 10384
Language: English
DOI: 10.1038/ncomms10384
PROVIDER: scopus
PMCID: PMC4735924
PUBMED: 26785948
Notes: Article -- Export Date: 3 March 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Laura Hong Tang
    382 Tang
  2. Xuejun Jiang
    98 Jiang