Investigation of the Role of Nck in Breast Cancer Cell Invasion and Invadopodia Formation and Its Interaction with ADAM19
Nck is an adaptor protein that has been implicated in cancer cell invasion and invadopodia formation. Nck is overexpressed in several breast cancer subtypes, and here we show that overexpression of Nck in MDA-MB-231 breast cancer cells increases 3D cell invasion, invadopodia formation and gelatin degradation. We also find that Nck interacts with ADAM19, another protein linked to invadopodia and invasion in several cancers. The ADAM19/Nck interaction can be disrupted by mutation of the first or possibly third SH3 domain of Nck. An inhibitor, AX-024, that binds to the unique DY pocket found in the first SH3 domain of Nck can reduce the invasion of breast cancer cells, possibly by disrupting the ADAM19/Nck interaction. Altogether, these results show that Nck signaling can promote breast cancer cell invasion and that the ADAM19/Nck interaction and more specifically the DY pocket is an intriguing target for the reduction of cancer cell metastasis.