Slug inhibits the proliferation and tumor formation of human cervical cancer cells by up-regulating the p21/p27 proteins and down-regulating the activity of the Wnt/β-catenin signaling pathway via the trans-suppression Akt1/p-Akt1 expression

Oncotarget. 2016 May 3;7(18):26152-67. doi: 10.18632/oncotarget.8434.

Abstract

Slug (Snai2) has been demonstrated to act as an oncogene or tumor suppressor in different human cancers, but the function of Slug in cervical cancer remains poorly understood. In this study, we demonstrated that Slug could suppress the proliferation of cervical cancer cells in vitro and tumor formation in vivo. Further experiments found that Slug could trans-suppress the expression of Akt1/p-Akt1 by binding to E-box motifs in the promoter of the Akt1 gene and then inhibit the cell proliferation and tumor formation of cervical cancer cells by up-regulating p21/p27 and/or down-regulating the activity of the Wnt/β-catenin signaling pathway. Therefore, Slug acts as a tumor suppressor during cervical carcinogenesis.

Keywords: Akt1; cervical cancer; proliferation; slug; wnt/β-catenin.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism*
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Xenograft Model Antitumor Assays
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Biomarkers, Tumor
  • CDKN1A protein, human
  • CDKN1B protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Wnt Proteins
  • beta Catenin
  • Cyclin-Dependent Kinase Inhibitor p27
  • Proto-Oncogene Proteins c-akt