Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β-catenin signaling pathway in breast cancer

Cancer Med. 2018 Aug;7(8):3875-3888. doi: 10.1002/cam4.1568. Epub 2018 Jul 2.

Abstract

Breast cancer was the highest incidence of tumor in women, which seriously threaten women's health. Our previous study found that the expression of IQUB (IQ motif and ubiquitin domain containing) was significantly increased in the development of breast cancer by transcriptome sequencing. However, there were no studies on the mechanism of IQUB in tumorigenesis. Further study showed that IQUB expression was significantly increased in breast cancer, which had a significantly positive correlation with pathological differentiation of breast cancer by tissue microarray analysis. Furthermore, we also discovered that IQUB overexpression could obviously promote the proliferation and migration of MCF-7 cells and increase the proportion of MCF-7 cells in S and G2/M phase in vitro study, while knockdown of IQUB caused inhibition of cell proliferation and migration in MDA-MB-231 cells and increased the proportion of MDA-MB-231 cells in G1 phase. Furthermore, IQUB overexpression or knockdown combined with treatment of Licl or MG-132 showed that IQUB activated Akt to promote GSK3β phosphorylation, which in turn activated Wnt/β-catenin signaling pathway in breast cancer cells. Taken together, these results indicated that upregulated IQUB promoted breast cancer cell proliferation and migration via activating Akt/GSK3β/β-catenin signaling pathway, which played an important part in the tumorigenesis and development of breast cancer.

Keywords: Akt/GSK3β/β-catenin signaling pathway; IQ motif and ubiquitin domain containing; breast cancer; cell migration; cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics
  • Biomarkers, Tumor*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Models, Biological
  • Neoplasm Grading
  • Neoplasm Staging
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*

Substances

  • Biomarkers, Tumor
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt