Increased galectin-3 facilitates leukemia cell survival from apoptotic stimuli
Increased galectin-3 facilitates leukemia cell survival from apoptotic stimuli
复制标题
DOI：
10.1016/j.bbrc.2011.07.099
复制
发表时间：
2011-08-26
影响因子：
3.1
通讯作者：
Lin, Chiou-Feng
中科院分区：
文献类型：
--
作者：
Cheng, Yi-Lin;Huang, Wei-Ching;Lin, Chiou-Feng
半乳糖凝集素-3调节癌细胞存活和凋亡，这取决于细胞类型和刺激。我们研究了糖原合成酶激酶（GSK）-3 β/半乳糖凝集素-3调节机制，用于白血病细胞逃避凋亡刺激。半乳糖凝集素-3的表达是时间和转录依赖性失调的K562慢性髓性白血病细胞刺激细胞凋亡顺铂（铂类化疗药物），鞘脂神经酰胺类似物C-2-神经酰胺，和LY 294002（磷脂酰肌醇3-激酶抑制剂）。值得注意的是，半乳糖凝集素-3在存活细胞中上调。强制半乳糖凝集素-3的表达引起抗凋亡，而敲低半乳糖凝集素-3的表达增加对凋亡的易感性。诱导型半乳糖凝集素-3的亚细胞分布是拟南芥特异性的。凋亡刺激降低促生存Bcl-2家族蛋白表达（特别是Mcl-1），而半乳糖凝集素-3过表达逆转，但它增强了半乳糖凝集素-3表达敲低。在细胞凋亡刺激下，GSK-3 β在Akt失活后被激活，GSK-3 β被抑制或使用短发夹RNA以消除半乳糖凝集素-3，增加细胞凋亡，并抑制集落形成，这表明GSK-3 β的促存活作用。我们发现GSK-3 β上调半乳糖凝集素-3和稳定抗凋亡Bcl-2家族蛋白，这对于白血病细胞逃避凋亡刺激是重要的。(C)2011 Elsevier Inc. All rights reserved.
Galectin-3 is regulated for cancer cell survival and apoptosis depending upon the cell type and stimulus. We investigated a glycogen synthase kinase (GSK)-3 beta/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 C-2-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-3 beta was activated after Akt was inactivated and GSK-3 beta 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-3 beta. We found that GSK-3 beta upregulated galectin-3 and stabilized anti-apoptotic Bcl-2 family proteins, which is important for the escape of leukemia cells from apoptotic stimuli. (C) 2011 Elsevier Inc. All rights reserved.