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Updated: Aug 24, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

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

Published on: December 27, 2016

Apoptosis initiated by dependence receptors: a new paradigm for cell death?

Alan G Porter1, Saravanakumar Dhakshinamoorthy

  • 1Institute of Molecular and Cell Biology, Republic of Singapore. mcbagp@imcb.a-star.edu.sg

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|June 2, 2004
PubMed

Insights

Dependence receptors like DCC and UNC5 regulate neuronal survival by inducing apoptosis when ligands are absent. This novel cell death mechanism is crucial for neural development and cancer suppression.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Cancer Biology

Background:

  • Certain receptors, including DCC, UNC5, RET, and Ptc1, mediate ligand-dependent neuronal growth, differentiation, and axon guidance.
  • These receptors can also function as "dependence receptors," inducing apoptosis in the absence of their cognate ligands.

Purpose of the Study:

  • To elucidate the mechanism of receptor-initiated apoptosis and its role in neuronal cell survival and cancer.
  • To explore the implications of dysfunctional dependence receptors in neurodegenerative diseases and cancer.

Main Methods:

  • Investigated receptor-initiated apoptosis involving caspase cleavage and pro-apoptotic region exposure.
  • Analyzed the role of DCC, UNC5, RET, and Ptc1 in neuronal cell death and survival signaling.
  • Examined the association of these receptors with cancer and neurodegenerative conditions.

Main Results:

  • Receptor-initiated apoptosis, distinct from classical apoptosis, requires proteolytic cleavage of dependence receptors.
  • Downregulation or mutation of DCC, UNC5, RET, and Ptc1 in cancers suggests tumor suppressor properties.
  • Dysfunctional dependence receptors are implicated in neuronal loss in inherited and neurodegenerative diseases.

Conclusions:

  • Dependence receptor-initiated apoptosis offers a novel mechanism for controlled cell removal during neural development.
  • This pathway is critical for eliminating malignant cells that have lost ligand dependency.
  • Understanding dependence receptors provides insights into neurodevelopment, neurodegeneration, and cancer biology.

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