Anderson, S., Poudel, K.R., Roh-Johnson, M., Brabletz, T., Yu, M., Borenstein-Auerbach, N., Grady, W.N., Bai, J., Moens, C.B., Eisenman, R.N., Conacci-Sorrell, M. (2016) MYC-nick promotes cell migration by inducing fascin expression and Cdc42 activation. Proceedings of the National Academy of Sciences of the United States of America. 113(37):E5481-90.
MYC-nick is a cytoplasmic, transcriptionally inactive member of the MYC oncoprotein family, generated by a proteolytic cleavage of full-length MYC. MYC-nick promotes migration and survival of cells in response to chemotherapeutic agents or withdrawal of glucose. Here we report that MYC-nick is abundant in colonic and intestinal tumors derived from mouse models with mutations in the Wnt, TGF-β, and PI3K pathways. Moreover, MYC-nick is elevated in colon cancer cells deleted for FBWX7, which encodes the major E3 ligase of full-length MYC frequently mutated in colorectal cancers. MYC-nick promotes the migration of colon cancer cells assayed in 3D cultures or grown as xenografts in a zebrafish metastasis model. MYC-nick accelerates migration by activating the Rho GTPase Cdc42 and inducing fascin expression. MYC-nick, fascin, and Cdc42 are frequently up-regulated in cells present at the invasive front of human colorectal tumors, suggesting a coordinated role for these proteins in tumor migration.