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

Soyoung Choi, Zhengming Chen, Laura H. Tang, Yuanzhang Fang, Sandra J. Shin, Nicole C. Panarelli, Yao Tseng Chen, Yi Li, Xuejun Jiang, Yi Chieh Nancy Du

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Article number10384
JournalNature Communications
Volume7
DOIs
StatePublished - Jan 20 2016
Externally publishedYes

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Mitochondria
mitochondria
metastasis
Neoplasm Metastasis
cancer
apoptosis
Cells
Apoptosis
nuclei
Epithelial-Mesenchymal Transition
Neuroendocrine Tumors
cultured cells
Heterografts
Epigenomics
breast
mice
Tumors
Neoplasms
Cell Survival
tumors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Choi, S., Chen, Z., Tang, L. H., Fang, Y., Shin, S. J., Panarelli, N. C., ... Du, Y. C. N. (2016). Bcl-xL promotes metastasis independent of its anti-apoptotic activity. Nature Communications, 7, [10384]. https://doi.org/10.1038/ncomms10384

Bcl-xL promotes metastasis independent of its anti-apoptotic activity. / Choi, Soyoung; Chen, Zhengming; Tang, Laura H.; Fang, Yuanzhang; Shin, Sandra J.; Panarelli, Nicole C.; Chen, Yao Tseng; Li, Yi; Jiang, Xuejun; Du, Yi Chieh Nancy.

In: Nature Communications, Vol. 7, 10384, 20.01.2016.

Research output: Contribution to journalArticle

Choi, S, Chen, Z, Tang, LH, Fang, Y, Shin, SJ, Panarelli, NC, Chen, YT, Li, Y, Jiang, X & Du, YCN 2016, 'Bcl-xL promotes metastasis independent of its anti-apoptotic activity', Nature Communications, vol. 7, 10384. https://doi.org/10.1038/ncomms10384
Choi, Soyoung ; Chen, Zhengming ; Tang, Laura H. ; Fang, Yuanzhang ; Shin, Sandra J. ; Panarelli, Nicole C. ; Chen, Yao Tseng ; Li, Yi ; Jiang, Xuejun ; Du, Yi Chieh Nancy. / Bcl-xL promotes metastasis independent of its anti-apoptotic activity. In: Nature Communications. 2016 ; Vol. 7.
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