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

Sarah Anderson, Kumud Raj Poudel, Minna Roh-Johnson, Thomas Brabletz, Ming Yu, Nofit Borenstein-Auerbach, William N. Grady, Jihong Bai, Cecilia B. Moens, Robert N. Eisenman, Maralice Conacci-Sorrell

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E5481-E5490
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number37
DOIs
StatePublished - Sep 13 2016

Keywords

  • Colon cancer
  • Fascin
  • MYC
  • MYC-nickm
  • Motility

ASJC Scopus subject areas

  • General

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