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ZIRC
ZFIN ID: ZDB-PUB-160828-2
MYC-nick promotes cell migration by inducing fascin expression and Cdc42 activation
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.
Date: 2016
Source: Proceedings of the National Academy of Sciences of the United States of America 113(37): E5481-90 (Journal)
Registered Authors: Moens, Cecilia
Keywords: MYC, MYC-nick, colon cancer, fascin, motility
MeSH Terms:
  • Animals
  • Carrier Proteins/genetics*
  • Cell Line, Tumor
  • Cell Movement/genetics
  • Colorectal Neoplasms/genetics*
  • Colorectal Neoplasms/pathology
  • F-Box-WD Repeat-Containing Protein 7/genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Microfilament Proteins/genetics*
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins c-myc/genetics*
  • Signal Transduction
  • Stomach Neoplasms/genetics*
  • Stomach Neoplasms/pathology
  • Transcriptional Activation/genetics
  • Zebrafish
  • cdc42 GTP-Binding Protein/genetics*
PubMed: 27566402 Full text @ Proc. Natl. Acad. Sci. USA
FIGURES
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.
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