Journal
ONCOGENE
Volume 29, Issue 14, Pages 2130-2141Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.491
Keywords
BI-1; cancer; metastasis; NHE; acidic pH
Funding
- Ministry of Education, Science and Technology, South Korea
- Ministry for Health, Welfare and Family Affairs, Republic of Korea [A084144]
Ask authors/readers for more resources
The anti-apoptotic protein, BAX inhibitor-1 (BI-1), has a role in cancer/tumor progression. BI-1-overexpressing HT1080 and B16F10 cells produced higher lung weights and tumor volumes after injection into the tail veins of mice. Transfection of BI-1 siRNA into cells before injection blocked lung metastasis. in vitro, the overexpression of BI-1 increased cell mobility and invasiveness, with highly increased glucose consumption and cytosolic accumulation of lactate and pyruvate, but decreased mitochondrial O(2) consumption and ATP production. Glucose metabolism-associated extracellular pH also decreased as cells excreted more H(+), and sodium hydrogen exchanger (NHE) activity increased, probably as a homeostatic mechanism for intracellular pH. These alterations activated MMP 2/9 and cell mobility and invasiveness, which were reversed by the NHE inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA), suggesting a role for NHE in cancer metastasis. In both in vitro and in vivo experiments, C-terminal deleted (CDBI-1) cells showed similar results to control cells, suggesting that the C-terminal motif is required for BI-1-associated alterations of glucose metabolism, NHE activation and cancer metastasis. These findings strongly suggest that BI-1 reduces extracellular pH and regulates metastasis by altering glucose metabolism and activating NHE, with the C-terminal tail having a pivotal role in these processes. Oncogene (2010) 29, 2130-2141; doi: 10.1038/onc.2009.491; published online 1 February 2010
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available