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Updated: Jul 17, 2025

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

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Regulation of anoikis by extrinsic death receptor pathways

Ying-Hao Han1, Yuan Wang2, Seung-Jae Lee3,4

  • 1College of Life Science & Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. hyhbynd@163.com.

Cell Communication and Signaling : CCS
|September 4, 2023
PubMed

Insights

Metastatic cancer cells resist anoikis (cell death without substrate) via death receptor pathways. These external pathways, particularly caspase-8-dependent ones, are crucial for tumor survival and metastasis.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Anoikis, a form of programmed cell death, is triggered by the detachment of anchorage-dependent cells from the extracellular matrix.
  • Metastatic cancer cells often acquire resistance to anoikis, enabling their survival and dissemination.
  • Both intrinsic (mitochondria-dependent) and extrinsic (death receptor-mediated) pathways regulate anoikis, with extrinsic pathways playing a more dominant role.

Discussion:

  • This review focuses on the extrinsic death receptor pathways regulating anoikis.
  • Key death receptors like Fas, TNFR1, DR4, and DR5 initiate signaling cascades upon ligand binding.
  • Mechanisms involve the recruitment of adaptor proteins such as FADD and TRADD, leading to downstream caspase activation.

Key Insights:

  • Caspase-8-dependent extrinsic pathways are critical for anoikis resistance in metastatic cancer.
  • Specific death receptor-ligand interactions and subsequent adaptor protein recruitment are central to this process.
  • Understanding these pathways offers insights into anoikis regulation and tumor progression.

Outlook:

  • Further research into death receptor pathway modulation could reveal novel therapeutic targets for cancer metastasis.
  • Investigating the precise molecular interactions within these pathways may uncover new strategies to overcome anoikis resistance.
  • This review provides a foundation for future studies on the role of death receptors in tumor metastasis.
Keywords:
AanoikisCancer metastasisDR4/DR5Death receptor pathwayFasTNFR1/TNFR2

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