Cancer development, chemoresistance, epithelial to mesenchymal transition and stem cells: A snapshot of IL-6 mediated involvement

Cancer Lett. 2016 May 28;375(1):51-61. doi: 10.1016/j.canlet.2016.02.048. Epub 2016 Mar 2.

Abstract

Interleukin-6 (IL-6) is a cytokine present in tumor microenvironment. Elevated level of IL-6 is associated with cancer cell proliferation, angiogenesis and metastasis through fueling STAT3, MAPK and Akt signaling. It promotes epithelial to mesenchymal transition (EMT) through altered expression of N-cadherin, vimentin, snail, twist and E-cadherin leading to cancer metastasis. IL-6 boosts mammosphere formation, self-renewal of stem cells, stemness properties of cancer cells and recruitment of mesenchymal stem cells. IL-6 is also a contributing factor for multidrug resistance in cancer due to gp130/MAPK/STAT3 mediated activation of transcription factors C/EBPβ/δ, overexpression of p-glycoprotein, EMT transition and expansion of stem cells. The in-depth investigation of IL-6 mediated cellular effects and its signaling pathway can provide the new window for future research and clinical development of IL-6 targeted therapy in cancer. Thus, an overview is delivered in this review deciphering the emerging aspect of the predominant influence of IL-6 in malignant transformation, EMT, cancer-associated stem cells and chemoresistance.

Keywords: Cancer stem cell; Chemoresistance and EMT; Cytokine; IL-6.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology*
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Interleukin-6 / physiology*
  • Neoplastic Stem Cells / metabolism*
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • IL6 protein, human
  • Interleukin-6