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Updated: Nov 25, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects

Portia Gough1, Ian A Myles1

  • 1Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, United States.

Frontiers in Immunology
|December 16, 2020
PubMed

Insights

Tumor Necrosis Factor-alpha (TNFα) signals through TNFR1 and TNFR2 receptors, triggering diverse cellular responses like apoptosis and NF-κB activation. This review details these pathways and their in vivo implications in immunity and cancer.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Biology

Background:

  • Tumor Necrosis Factor-alpha (TNFα), discovered in 1975, is crucial in immunity and cancer.
  • TNFα exhibits pleiotropic signaling through its receptors, TNFR1 and TNFR2.
  • Understanding TNFα's diverse cellular effects (proliferation, survival, apoptosis, necrosis) is vital for disease research.

Purpose of the Study:

  • To elucidate the intracellular signaling pathways initiated by TNFα via TNFR1 and TNFR2.
  • To detail the distinct signaling complexes leading to canonical/non-canonical NF-κB activation, apoptosis, and necrosis.
  • To analyze in vivo data from mouse and human studies on TNFR1 versus TNFR2 signaling impacts.

Main Methods:

  • Review of existing literature on TNFα signaling pathways.
  • Analysis of signaling complexes formed by TNFR1 and TNFR2.
  • Examination of in vivo studies investigating TNFR1 and TNFR2 functions.

Main Results:

  • Detailed description of signaling complexes mediating cellular responses.
  • Explanation of canonical and non-canonical NF-κB activation pathways.
  • Discussion of differential roles of TNFR1 and TNFR2 signaling in vivo.

Conclusions:

  • TNFα's dual receptor engagement dictates varied cellular outcomes.
  • Intracellular signaling mechanisms are key to understanding TNFα's role in disease.
  • Further research into TNFR1/TNFR2 differential signaling is warranted for therapeutic insights.
Keywords:
NF-kappa BTNFTNF blockadeTNF receptorepithelial to mesenchymal transitionsignaling/signaling pathways

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