Gao Xiaoge, Balan Vitaly, Tai Guihua, Raz Avraham
¹Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. ²School of Life Sciences, Northeast Normal University, Changchun, PR China.
Oncotarget. 2014 Apr 30;5(8):2077-84. doi: 10.18632/oncotarget.1786.
The presence and level of circulating galectin-3 (Gal-3), a member of the galectin family, is associated with diverse diseases ranging from heart failure, immune disorders to cancer metastasis and serves as a biomarker of diagnosis and treatment response. However, the mechanisms by which exogenous Gal-3 affects pathobiology events remain elusive. In the current study, we found that exogenous Gal-3 slightly delays, while prolonging tyrosine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in HeLa cells through a calcium-sensitive and PKC-dependent signaling pathway. The activation was dependent on the sugar-binding properties of Gal-3, since the antagonist lactose could inhibit it. The sugar-binding motif of Gal-3 was required for the activation of ERK1/2. The activation of ERK1/2 was necessary for the initiation and induction of cell migration associated with the phosphorylation of paxillin. All the results presented in this study suggest a novel calcium-sensitive and PKC-dependent pathway through which circulating Gal-3 promotes cell migration and activating the ERK1/2. Taken together, the data depicted here propose a biological function and a target for the diseases' associated circulating Gal-3.
半乳糖凝集素-3（Gal-3）是半乳糖凝集素家族的一员，其在循环系统中的存在及水平与多种疾病相关，包括心力衰竭、免疫紊乱乃至癌症转移，并且可作为诊断和治疗反应的生物标志物。然而，外源性Gal-3影响病理生物学事件的机制仍不清楚。在本研究中，我们发现外源性Gal-3通过钙敏感且依赖蛋白激酶C（PKC）的信号通路，略微延迟但延长了HeLa细胞中细胞外信号调节激酶1/2（ERK1/2）的酪氨酸磷酸化。这种激活依赖于Gal-3的糖结合特性，因为拮抗剂乳糖可以抑制它。Gal-3的糖结合基序是ERK1/2激活所必需的。ERK1/2的激活对于与桩蛋白磷酸化相关的细胞迁移的起始和诱导是必要的。本研究中呈现的所有结果表明，存在一种新的钙敏感且依赖PKC的信号通路，循环中的Gal-3通过该通路促进细胞迁移并激活ERK1/2。综上所述，此处描述的数据揭示了循环Gal-3的一种生物学功能以及针对相关疾病的一个靶点。
