Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells
Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells
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DOI：
10.1038/onc.2010.631
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发表时间：
2011-06-01
期刊：
影响因子：
8
通讯作者：
Pigny, P.
中科院分区：
文献类型：
--
作者：
Merlin, J.;Stechly, L.;Pigny, P.
MUC1是一种跨膜糖蛋白，通常在正常上皮细胞的顶膜表达。在癌细胞中，MUC1的过度表达及其在细胞膜和细胞质中的异常定位有利于其与不同的蛋白质伙伴如表皮生长因子受体(EGFR)相互作用，并通过激活致癌信号通路促进肿瘤的增殖。我们的目的是研究诱导胰腺癌细胞MUC1胞浆定位的机制，并破译它们对EGFR细胞定位和激活的影响。我们的结果表明，Galectin-3是一种内源性凝集素，在人胰腺导管腺癌中与MUC1共表达，并有利于MUC1和EGFR的内吞。RNA干扰去除Galectin-3后，MUC1与EGFR、EGFR与ERK-1，2磷酸化之间的相互作用增加，EGFR移位至胞核。相反，Galectin-3沉默导致细胞周期蛋白-D_1水平下降，细胞增殖受阻。Galectin-3对MUC1/EGFR功能的依赖调节可能代表了一种有趣的机制，它调节了EGFR刺激的胰腺癌细胞的生长。Oncogene(2010)30,2514-2525；doi：10.1038/onc.2010.631；2011年1月24日在线发布
MUC1 is a transmembrane glycoprotein which is typically expressed at the apical membrane of normal epithelial cells. In cancer cells, the over-expression of MUC1 and its aberrant localization around the cell membrane and in the cytoplasm favours its interaction with different protein partners such as epidermal growth factor receptor (EGFR) and can promote tumour proliferation through the activation of oncogenic signalling pathways. Our aims were to study the mechanisms inducing MUC1 cytoplasmic localization in pancreatic cancer cells, and to decipher their impact on EGFR cellular localization and activation. Our results showed that galectin-3, an endogenous lectin, is co-expressed with MUC1 in human pancreatic ductal adenocarcinoma, and that it favours the endocytosis of MUC1 and EGFR. Depletion of galectin-3 by RNA interference increased the interaction between MUC1 and EGFR, EGFR and ERK-1,2 phosphorylation, and translocation of EGFR to the nucleus. On the contrary, silencing of galectin-3 led to a decrease of cyclin-D1 levels and of cell proliferation. The galectin-3-dependent regulation of MUC1/EGFR functions may represent an interesting mechanism modulating the EGFR-stimulated cell growth of pancreatic cancer cells. Oncogene (2010) 30, 2514-2525; doi: 10.1038/onc.2010.631; published online 24 January 2011