Étude du rôle de l'adaptateur Nck2 dans la progression métastatique du mélanome humain
The metastatic process is highly fatal in many cancers, including human melanoma. Metastatic progression is a multistep process in which cytoskeletal organization allows migration and invasion of cancer cells. Nck2 is an adaptor protein mainly associated with cytoskeletal organization. A preliminary study carried out in our laboratory has shown that Nck2 protein and mRNA levels are increased in metastatic melanoma cell lines compared to primary cell lines. In this study, the role of Nck2 in metastatic progression was further investigated. Results confirmed that Nck2 levels are increased in metastatic melanoma compared to primary cell lines. Nck2 overexpression in primary melanoma induced migration and cell proliferation, did not affect invasion in type I collagen matrix, but decreased cell-cell and cell-substrate adhesion. In addition, a preliminary in vivo study suggested that Nck2 overexpression slightly increased tumorigenesis and tumor growth in primary melanoma. All together, these results indicate that Nck2 may effectively influence metastatic progression of melanoma by increasing cancer cell proliferation and detachment from the primary tumor, allowing them to enter the blood circulation and form distant colonies. At the molecular level, we propose that Nck2 is recruited to invadopodia in order to form molecular complexes that increase cell invasion, and this may results in a decrease in Nck2 levels available to form other molecular complexes in others cell compartments, such as focal adhesions (FA) and adherent cell junctions.
Nck2 Adaptator protein Human melanoma