Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo

BMC Cancer

Research Article

Peter M Siegel¹  Julie Dusseault²  Aude Picard-Cloutier²  Louise Larose²  Salma Ismaïl²  Mélissa Labelle-Côté³ 

[1] Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada;Polypeptide Laboratory, Division of Endocrinology, Department of Medicine and Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada;Programmes de biologie moléculaire, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada;Polypeptide Laboratory, Division of Endocrinology, Department of Medicine and Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada;

关键词: Melanoma;    Melanoma Cell;    Focal Adhesion Kinase;    Melanoma Cell Line;    Human Melanoma Cell;   

DOI  :  10.1186/1471-2407-11-443

 received in 2011-07-27, accepted in 2011-10-12,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundNck1 and Nck2 adaptor proteins are involved in signaling pathways mediating proliferation, cytoskeleton organization and integrated stress response. Overexpression of Nck1 in fibroblasts has been shown to be oncogenic. Through the years this concept has been challenged and the consensus is now that overexpression of either Nck cooperates with strong oncogenes to transform cells. Therefore, variations in Nck expression levels in transformed cells could endorse cancer progression.MethodsExpression of Nck1 and Nck2 proteins in various cancer cell lines at different stages of progression were analyzed by western blots. We created human primary melanoma cell lines overexpressing GFP-Nck2 and investigated their ability to proliferate along with metastatic characteristics such as migration and invasion. By western blot analysis, we compared levels of proteins phosphorylated on tyrosine as well as cadherins and integrins in human melanoma cells overexpressing or not Nck2. Finally, in mice we assessed tumor growth rate of human melanoma cells expressing increasing levels of Nck2.ResultsWe found that expression of Nck2 is consistently increased in various metastatic cancer cell lines compared with primary counterparts. Particularly, we observed significant higher levels of Nck2 protein and mRNA, as opposed to no change in Nck1, in human metastatic melanoma cell lines compared with non-metastatic melanoma and normal melanocytes. We demonstrated the involvement of Nck2 in proliferation, migration and invasion in human melanoma cells. Moreover, we discovered that Nck2 overexpression in human primary melanoma cells correlates with higher levels of proteins phosphorylated on tyrosine residues, assembly of Nck2-dependent pY-proteins-containing molecular complexes and downregulation of cadherins and integrins. Importantly, we uncovered that injection of Nck2-overexpressing human primary melanoma cells into mice increases melanoma-derived tumor growth rate.ConclusionsCollectively, our data indicate that Nck2 effectively influences human melanoma phenotype progression. At the molecular level, we propose that Nck2 in human primary melanoma promotes the formation of molecular complexes regulating proliferation and actin cytoskeleton dynamics by modulating kinases or phosphatases activities that results in increased levels of proteins phosphorylated on tyrosine residues. This study provides new insights regarding cancer progression that could impact on the therapeutic strategies targeting cancer.

【 授权许可】

Unknown   
© Labelle-Côté et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.