Resistin causes G1 arrest in colon cancer cells through upregulation of SOCS3

FEBS Lett. 2017 May;591(10):1371-1382. doi: 10.1002/1873-3468.12655. Epub 2017 May 6.

Abstract

Resistin, a proinflammatory cytokine, is elevated in a number of pathological disorders, including cancer. The serum resistin level in colon cancer patients is elevated and correlates with tumor grade. However, the implications of increased resistin on colon cancer cells remain unclear. In the present study, we find that resistin binds to TLR4 on colon cancer cell membrane and initiates TLR4-MyD88-dependent activation of ERK. In addition, the upregulation of SOCS3 by ERK downregulates the JAK2/TAT3 pathway and causes the arrest of cells in G1 phase. Interestingly, we observe that resistin-exposed cells survive 5-fluorouracil treatment because of a decrease in drug uptake due to the arrest of cells in G1 phase.

Keywords: SOCS3; TLR4; colon cancer; resistin.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Janus Kinase 2 / metabolism
  • MAP Kinase Signaling System
  • Resistin / genetics
  • Resistin / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Suppressor of Cytokine Signaling 3 Protein / genetics*
  • Toll-Like Receptor 4 / metabolism*
  • Up-Regulation*

Substances

  • RETN protein, human
  • Resistin
  • SOCS3 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • JAK2 protein, human
  • Janus Kinase 2