GDF15 Promotes EMT and Metastasis in Colorectal Cancer

Oncotarget. 2016 Jan 5;7(1):860-72. doi: 10.18632/oncotarget.6205.

Abstract

Metastasis is the major cause of cancer deaths, and the epithelial-mesenchymal transition (EMT) has been considered to be a fundamental event in cancer metastasis. However, the role of growth differentiation factor 15 (GDF15) in colorectal cancer (CRC) metastasis and EMT remains poorly understood. Here, we showed that GDF15 promoted CRC cell metastasis both in vitro and in vivo. In addition, the EMT process was enhanced by GDF15 through binding to TGF-β receptor to activate Smad2 and Smad3 pathways. Clinical data showed GDF15 level in tumor tissues, and the serum was significantly increased, in which high GDF15 level correlated with a reduced overall survival in CRC. Thus, GDF15 may promote colorectal cancer metastasis through activating EMT. Promisingly, GDF15 could be considered as a novel prognostic marker for CRC in the clinic.

Keywords: EMT; GDF15; colorectal cancer; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Growth Differentiation Factor 15 / blood
  • Growth Differentiation Factor 15 / genetics*
  • Growth Differentiation Factor 15 / metabolism
  • HEK293 Cells
  • HT29 Cells
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Neoplasm Metastasis
  • Proportional Hazards Models
  • RNA Interference
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / statistics & numerical data
  • Smad2 Protein / genetics
  • Smad2 Protein / metabolism
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism
  • Survival Analysis
  • Transplantation, Heterologous

Substances

  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Receptors, Transforming Growth Factor beta
  • Smad2 Protein
  • Smad3 Protein