Unfolding transmembrane TNFα dynamics in cancer therapeutics

Cytokine. 2021 Jan:137:155303. doi: 10.1016/j.cyto.2020.155303. Epub 2020 Sep 29.

Abstract

Cytokines are a group of glycoprotein signaling mediators, which play essential roles in maintaining several complex physiological functions of our body. TNFα is such a pleiotropic cytokine, which involves maintaining a plethora of immune responses. Initially, TNFα is synthesized as a 26 kDa full-length transmembrane form, which is enzymatically cleaved to produce the soluble circulating 17 kDa TNFα. Although the anti-cancer potential of soluble TNFα was discovered more than a century back, its dual ability to promote tumor, posed a major hindrance in finding its acceptance as a proper anti-cancer molecule. In contrast, the membrane-tethered tmTNFα holds the potential of tumor regression without initiating cell proliferation. The membrane-tethered form of TNFα is the physiological precursor of soluble TNFα that remains biologically active and is capable of initiating signaling cascades after binding with the TNFα receptors- TNFR I and TNFR II. In this review, we emphasize on the basic biology and molecular aspects of tmTNFα for its anti-cancer potential.

Keywords: Apoptosis; Cancer; Cytotoxicity; Transmembrane tumor necrosis factor α (tmTNFα).

Publication types

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

MeSH terms

  • Apoptosis / immunology*
  • Cytotoxicity, Immunologic / immunology*
  • Humans
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Binding
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Receptors, Tumor Necrosis Factor, Type II / metabolism
  • Signal Transduction / immunology*
  • Tumor Necrosis Factor-alpha / immunology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • TNFRSF1B protein, human
  • Tumor Necrosis Factor-alpha