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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

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Central Signaling Elements of Intercellular Reactive Oxygen/Nitrogen Species-dependent Induction of Apoptosis in

Georg Bauer1

  • 1Institute of Virology, Medical Faculty, University Medical Center Freiburg, Freiburg, Germany georg.bauer@uniklinik-freiburg.de.

Anticancer Research
|February 10, 2017
PubMed

Insights

Intercellular reactive oxygen/nitrogen species (ROS/RNS) signaling induces apoptosis in malignant cells. Transforming growth factor β1 and NADPH oxidase 1 pathways are key regulators, utilizing mitochondrial apoptosis pathways.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Intercellular reactive oxygen/nitrogen species (ROS/RNS) signaling is implicated in cancer development.
  • Previous studies relied on inhibitors and scavengers to understand apoptosis induction mechanisms.

Purpose of the Study:

  • To elucidate the molecular mechanisms of intercellular ROS/RNS-dependent apoptosis induction.
  • To identify key signaling players in oncogenesis control.

Main Methods:

  • Small interfering ribonucleic acid (siRNA)-mediated knockdown of apoptosis pathway components.
  • Analysis of mitochondrial and FAS receptor-dependent apoptosis pathways.

Main Results:

  • Transforming growth factor β1, its receptor, NADPH oxidase-1 (NOX1), NOX1 organizer, and NOX1 activator regulate HOCl and NO/peroxynitrite signaling.
  • Dual oxidase-1 (DUOX1) mediates HOCl signaling, while NO synthase mediates NO/peroxynitrite signaling.
  • Both pathways converge on protein kinase C zeta, sphingomyelinase, and mitochondrial apoptosis pathways.

Conclusions:

  • Intercellular ROS/RNS signaling, particularly via TGF-β1 and NOX1, is crucial for apoptosis induction in malignant cells.
  • The FAS receptor pathway is not involved in this specific intercellular apoptosis signaling.
  • This signaling mechanism represents a potential control step during oncogenesis.
Keywords:
ApoptosisHOCl signalingNO/peroxynitrite signalingintercellular ROS/RNS signalingsmall interfering RNA

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