Galectin-1-Mediated Tumor Invasion and Metastasis, Up-Regulated Matrix Metalloproteinase Expression, and Reorganized Actin Cytoskeletons
Galectin-1-Mediated Tumor Invasion and Metastasis, Up-Regulated Matrix Metalloproteinase Expression, and Reorganized Actin Cytoskeletons
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DOI：
10.1158/1541-7786.mcr-08-0297
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发表时间：
2009-03-01
影响因子：
5.2
通讯作者：
Chen, Yuh-Ling
中科院分区：
文献类型：
--
作者：
Wu, Ming-Heng;Hong, Tse-Ming;Chen, Yuh-Ling
半乳糖凝集素-1 （Gal-1）是一种β -半乳糖结合凝集素；据报道其表达水平与肿瘤进展相关。在口腔鳞状细胞癌患者的淋巴结中，Gal-1在原发肿瘤的侵袭前和转移灶的癌细胞中高度表达。然而，Gal-1在肿瘤转移中的分子机制尚不完全清楚。我们发现，在肺腺癌和口腔鳞状细胞癌细胞系中，Gal-1表达的增加与其高水平的侵袭密切相关。用小干扰RNA敲除高侵袭性癌细胞中的Gal-1可降低其侵袭水平。此外，过表达Gal-1后，侵袭能力较差的癌细胞的侵袭能力明显增强。机制研究表明，Gal-1主要通过上调基质金属蛋白酶(MMP)-9和MMP-2以及重组肌动蛋白细胞骨架促进肿瘤侵袭。Gal-1增强了Rho家族的小GTPase Cdc42的激活，从而增加了肿瘤细胞上丝状足的数量和长度。此外，在体内高静脉转移试验中，过表达gal -1的细胞具有更高的转移能力。我们认为，在口腔癌和肺腺癌中，Gal-1通过增加MMP的表达和重组细胞骨架参与了肿瘤的侵袭和转移。[j] .癌症杂志，2009;7(3):311-8。
Galectin-1 (Gal-1) Is a beta-galactose-binding lectin; its expression level has been reported to correlate with tumor progression. Gal-1 is highly expressed In the Invasive front of primary tumors and in the cancer cells of metastatic lesions In the lymph nodes of patients with oral squamous cell carcinoma. However, the molecular mechanism of Gal-1 In tumor metastasis Is not completely clear. We found that Increased Gal-1 expression Is closely associated with Its high levels of invasion In lung adenocarcinoma and oral squamous cell carcinoma cell lines. Knocking down Gal-1 with small Interfering RNA In highly Invasive cancer cells reduced their Invasion levels. Moreover, the Invasion ability of poorly invasive cancer cells was significantly Increased after Gal-1 overexpression of Gal-1. Mechanism studies revealed that Gal-1 promoted tumor invasion mainly by up-regulating matrix metalloproteinase (MMP)-9 and MMP-2 and by reorganizing actin cytoskeleton. Gal-1 enhanced the activation of Cdc42, a small GTPase and member of the Rho family, thus Increasing the number and length of filopodia on tumor cells. Furthermore, Gal-1-overexpressing cells had higher metastatic abilities In tall vein metastasis assays in vivo. We conclude that Gal-1 Is Involved In tumor invasion and metastasis by increasing MMP expression and reorganizing cytoskeletons In oral cancers and lung adenocarcinoma. (Mol Cancer Res 2009;7(3):311-8)