Wong Ronald P C, Ng Philip, Dedhar Shoukat, Li Gang
Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Mol Cancer Ther. 2007 Jun;6(6):1692-700. doi: 10.1158/1535-7163.MCT-07-0134.
Melanoma is a life-threatening disease with a high mortality rate due to rapid metastasis. Currently, there is no effective treatment for metastatic melanoma. Integrin-linked kinase (ILK) is a serine/threonine kinase and has its role implicated in connecting cell-extracellular matrix interaction and growth factor signaling to cell survival, cell migration, invasion, anchorage-independent growth, angiogenesis, and epithelial-mesenchymal transition. However, the functional role of ILK in melanoma progression is not completely understood. We have previously shown that strong ILK expression was significantly associated with melanoma thickness. In this study, we further elucidate the role of ILK in melanoma cell migration, invasion, anchorage-independent growth, and tumor growth in vivo by specific ILK knockdown using small interfering RNA and short hairpin RNA. We found that ILK knockdown impeded melanoma cell migration, which was associated with reduced stress fiber formation, cell spreading, and cell adhesion. Furthermore, ILK knockdown decreased the invasion ability of melanoma cells and the formation of anchorage-independent colonies in soft agar. Moreover, ILK knockdown significantly impaired the growth of melanoma xenografts in severe combined immunodeficient mice. This study highlights the importance of ILK in melanoma progression and provides an attractive target for the treatment of melanoma.
黑色素瘤是一种因快速转移而死亡率高的危及生命的疾病。目前,转移性黑色素瘤尚无有效的治疗方法。整合素连接激酶(ILK)是一种丝氨酸/苏氨酸激酶,其作用涉及将细胞 - 细胞外基质相互作用和生长因子信号传导与细胞存活、细胞迁移、侵袭、非锚定依赖性生长、血管生成以及上皮 - 间质转化联系起来。然而,ILK在黑色素瘤进展中的功能作用尚未完全明确。我们之前已经表明,ILK的强表达与黑色素瘤厚度显著相关。在本研究中,我们通过使用小干扰RNA和短发夹RNA特异性敲低ILK,进一步阐明ILK在黑色素瘤细胞迁移、侵袭、非锚定依赖性生长以及体内肿瘤生长中的作用。我们发现,敲低ILK会阻碍黑色素瘤细胞迁移,这与应力纤维形成减少、细胞铺展和细胞黏附降低有关。此外,敲低ILK会降低黑色素瘤细胞的侵袭能力以及在软琼脂中形成非锚定依赖性集落的能力。而且,敲低ILK会显著损害严重联合免疫缺陷小鼠体内黑色素瘤异种移植物的生长。本研究突出了ILK在黑色素瘤进展中的重要性,并为黑色素瘤的治疗提供了一个有吸引力的靶点。