The role of integrin-linked kinase in melanoma cell migration, invasion, and tumor growth.
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.
Wong
Ronald P C
RP
Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Ng
Philip
P
Dedhar
Shoukat
S
Li
Gang
G
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009841:Oligonucleotides; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK
D009841:Oligonucleotides; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK