Snf1-related kinase inhibits colon cancer cell proliferation through calcyclin-binding protein-dependent reduction of β-catenin

Amy K. Rines, Michael A. Burke, Richard P. Fernandez, Olga V. Volpert, Hossein Ardehali*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Sucrose nonfermenting 1 (Snf1)-related kinase (SNRK) is a serine/threonine kinase with sequence similarity to AMP-activated protein kinase (AMPK); however, its function is not well characterized. We conducted a gene array to determine which genes are regulated by SNRK. The array demonstrated that SNRK overexpression increased the levels of genes involved in cell proliferation, including calcyclin-binding protein (CacyBP), a member of the ubiquitin ligase complex that targets nonphosphorylated β-catenin for degradation. We confirmed that SNRK increased CacyBP mRNA and protein, and decreased β-catenin protein in HCT116 and RKO colon cancer cells. Furthermore, SNRK inhibited colon cancer cell proliferation, and CacyBP down-regulation reversed the SNRK-mediated decrease in proliferation and β-catenin SNRK overexpression also decreased β-catenin nuclear localization and target gene transcription, and β-catenin down-regulation reversed the effects of SNRK knockdown on proliferation. SNRK transcript levels were reduced in human colon tumors compared to normal tissue by 35.82%, and stable knockdown of SNRK increased colon cancer cell tumorigenicity. Our results demonstrate that SNRK is down-regulated in colon cancer and inhibits colon cancer cell proliferation through CacyBP up-regulation and β-catenin degradation, resulting in reduced proliferation signaling. These findings reveal a novel function for SNRK in the regulation of colon cancer cell proliferation and β-catenin signaling.

Original languageEnglish (US)
Pages (from-to)4685-4695
Number of pages11
JournalFASEB Journal
Volume26
Issue number11
DOIs
StatePublished - Nov 2012

Keywords

  • CacyBP
  • SNRK

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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