Galectin-1 induces hepatocellular carcinoma EMT and sorafenib resistance by activating FAK/PI3K/AKT signaling.
Galectin-1 induces hepatocellular carcinoma EMT and sorafenib resistance by activating FAK/PI3K/AKT signaling.
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Galectin-1通过激活FAK/PI3K/AKT信号诱导肝细胞癌EMT和索拉非尼耐药
DOI：
10.1038/cddis.2015.324
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发表时间：
2016-04-21
影响因子：
9
通讯作者：
Shi GM
中科院分区：
文献类型：
--
作者：
Zhang PF;Li KS;Shen YH;Gao PT;Dong ZR;Cai JB;Zhang C;Huang XY;Tian MX;Hu ZQ;Gao DM;Fan J;Ke AW;Shi GM
半乳糖凝集素-1（Galectin-1，Gal-1）参与了多种与肿瘤进展和化疗耐药相关的病理活动，然而，Gal-1在肝细胞癌（HCC）上皮-间质转化（EMT）和索拉非尼耐药中的作用及其分子机制仍然是个谜。在本研究中，强制Gal-1表达促进HCC进展和索拉非尼耐药。Gal-1增加αvβ3-整合素表达，导致AKT活化。此外，Gal-1过表达通过PI 3 K/AKT级联激活诱导HCC细胞EMT。临床上，我们的数据显示，Gal-1过表达与HCC生存率和索拉非尼反应不良相关。这些数据表明，Gal-1可能是HCC的潜在治疗靶点和预测索拉非尼治疗反应的生物标志物。
Galectin-1 (Gal-1) is involved in several pathological activities associated with tumor progression and chemoresistance, however, the role and molecular mechanism of Gal-1 activity in hepatocellular carcinoma (HCC) epithelial–mesenchymal transition (EMT) and sorafenib resistance remain enigmatic. In the present study, forced Gal-1 expression promoted HCC progression and sorafenib resistance. Gal-1 elevated αvβ3-integrin expression, leading to AKT activation. Moreover, Gal-1 overexpression induced HCC cell EMT via PI3K/AKT cascade activation. Clinically, our data revealed that Gal-1 overexpression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that Gal-1 may be a potential therapeutic target for HCC and a biomarker for predicting response to sorafenib treatment.