Galectin-3 is regulated for cancer cell survival and apoptosis depending upon the cell type and stimulus. We investigated a glycogen synthase kinase (GSK)-3β/galectin-3-regulated mechanism used by leukemia cells to escape from apoptotic stimuli. Galectin-3 expression was time- and transcription-dependently deregulated in K562 chronic myeloid leukemia cells stimulated for apoptosis by cisplatin (a platinum-based chemotherapy drug), sphingolipid ceramide analog C2-ceramide, and LY294002 (a phosphatidylinositol 3-kinase inhibitor). Notably, galectin-3 was upregulated in survival cells. Forced galectin-3 expression caused resistance to apoptosis, whereas knockdown galectin-3 expression increased susceptibility to apoptosis. Sub-cellular distribution of inducible galectin-3 was mitochondria-specific. Apoptotic stimuli decreased pro-survival Bcl-2 family protein expression (especially Mcl-1), whereas galectin-3 overexpression reversed but it was enhanced by a galectin-3 expression knockdown. Under apoptotic stimulation, GSK-3β was activated after Akt was inactivated and GSK-3β was inhibited-either pharmacologically or using short hairpin RNA to abolish galectin-3, increase apoptosis, and inhibit colony formation-which suggests a pro-survival role for GSK-3β. We found that GSK-3β upregulated galectin-3 and stabilized anti-apoptotic Bcl-2 family proteins, which is important for the escape of leukemia cells from apoptotic stimuli.
|頁（從 - 到）||334-340|
|期刊||Biochemical and Biophysical Research Communications|
|出版狀態||已發佈 - 八月 26 2011|
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cheng, Y-L., Huang, W-C., Chen, C-L., Tsai, C-C., Wang, C-Y., Chiu, W-H., Chen, Y-L., Lin, Y-S., Chang, C-F., & Lin, C. F. (2011). Increased galectin-3 facilitates leukemia cell survival from apoptotic stimuli. Biochemical and Biophysical Research Communications, 412(2), 334-340. https://doi.org/10.1016/j.bbrc.2011.07.099