MYC-nick promotes cell migration by inducing fascin expression and Cdc42 activation.


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.

  • Anderson S
  • Bai J
  • Borenstein-Auerbach N
  • Brabletz T
  • Conacci-Sorrell M
  • Eisenman RN
  • Grady WN
  • Moens CB
  • Poudel KR
  • Roh-Johnson M
  • Yu M
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Appears In
Proc Natl Acad Sci U S A, 2016, 113 (37)