Nodal signaling modulates the expression of Oct-4 via nuclear translocation of β-catenin in lung and prostate cancer cells

Arch Biochem Biophys. 2016 Oct 15:608:34-41. doi: 10.1016/j.abb.2016.07.003. Epub 2016 Aug 31.

Abstract

Nodal is a member of transforming growth factor beta (TGF-β) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the β-catenin nuclear translocation. This increase was attributed to GSK-3β dephosphorylating, and activin receptor-like kinase 4/7 (ALK4/7) played a major role in human cancer cells. Our study provides a positive understanding of Nodal function in cancer cells and suggests a potential novel target for clinical therapeutic research.

Keywords: ALK4/7; Nodal; Oct-4; Wnt/β-catenin signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Active Transport, Cell Nucleus*
  • Activin Receptors, Type I / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cytoplasm / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Nodal Protein / metabolism*
  • Octamer Transcription Factor-3 / metabolism*
  • Prostatic Neoplasms / metabolism*
  • Signal Transduction
  • Transfection
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • NODAL protein, human
  • Nodal Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • beta Catenin
  • ACVR1B protein, human
  • Activin Receptors, Type I