GC-binding factor 2 interacts with dishevelled and regulates Wnt signaling pathways in human carcinoma cell lines

Hideo Ohtsuka, Masaya Oikawa, Kyohei Ariake, Toshiki Rikiyama, Fuyuhiko Motoi, Yu Katayose, Michiaki Unno, Alfred C. Johnson

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

GC-binding factor 2 (GCF2), a transcriptional repressor that decreases the activity of several genes is capable of binding directly to the GC-rich sequence of the EGFR promoter and repressing the transcriptional activity of EGFR. In addition to its function as a transcriptional repressor, GCF2 can directly interact with other proteins such as flightless-1 (Fli-1). Many previous findings pertaining to the function of Fli-1 have suggested a role for fli-1 in providing a direct link between molecules involved in signal transduction pathways and the actin cytoskeleton. We hypothesized that GCF2, together with Fli-1, plays a role in regulating cytoskeleton function, cell migration, and/or morphology. In our study, we observed that GCF2 is crucial for the activation of RhoA, a small GTPase that plays a key role in the regulation of the actin cytoskeleton. RhoA was markedly inactivated as a result of the decreased expression of GCF2. Co-immunoprecipitations were subsequently performed to further investigate the mechanism for the repressive function. We identified dishevelled (Dvl), which is the key mediator for the Wnt pathway, as a binding partner with GCF2. These results strongly suggest that GCF2 plays a role in the Wnt-noncanonical planar cell polarity (PCP) signaling pathway. Consequently, GCF2 may regulate the cytoskeleton or migration via Dvls and RhoA.

Original languageEnglish
Pages (from-to)1599-1610
Number of pages12
JournalInternational Journal of Cancer
Volume129
Issue number7
DOIs
Publication statusPublished - 2011 Oct 1

Keywords

  • GCF2
  • LRRFIP1
  • RhoA
  • Wnt
  • dishevelled
  • migration

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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