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Updated: Apr 28, 2026

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
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Redox modulation of FAK controls melanoma survival--role of NOX4

Cristiane Ribeiro-Pereira1, João Alfredo Moraes1, Mariele de Jesus Souza1

  • 1Laboratory of Cellular and Molecular Pharmacology, Department of Cell Biology, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Plos One
|June 10, 2014
PubMed

Insights

Reactive oxygen species (ROS) from NADPH oxidase are crucial for melanoma survival. This study reveals ROS, likely from NOX4, signals through FAK to maintain melanoma cell adhesion and viability.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Reactive oxygen species (ROS) produced by NADPH oxidase are vital for melanoma cell proliferation and survival.
  • The precise signaling mechanisms linking NADPH oxidase-derived ROS to melanoma cell fate remain largely undefined.

Purpose of the Study:

  • To investigate the role of NADPH oxidase-generated ROS in the signaling pathways governing melanoma cell survival.
  • To elucidate the specific NADPH oxidase isoform involved in maintaining melanoma cell viability.

Main Methods:

  • Utilized the human melanoma cell line MV3.
  • Employed pharmacological NADPH oxidase inhibition and NOX4 gene silencing.
  • Assessed melanoma cell viability, morphology, actin cytoskeleton dynamics, focal adhesion kinase (FAK) phosphorylation, and apoptosis markers (caspase-3 activation, hypodiploid DNA content).

Main Results:

  • Pharmacological inhibition of NADPH oxidase reduced melanoma cell viability and induced cytoskeletal changes, indicative of focal adhesion disassembly and potential anoikis.
  • Inhibition led to decreased FAK phosphorylation at Y397 and reduced association of FAK with actin and cSrc.
  • NOX4 silencing diminished basal ROS production, FAK Y397 phosphorylation, and melanoma cell viability.
  • NADPH oxidase inhibition increased hypodiploid DNA content and caspase-3 activation, signaling apoptosis.

Conclusions:

  • Intracellular ROS generated by NADPH oxidase, likely NOX4, are essential for melanoma cell survival.
  • These ROS transmit survival signals via the FAK pathway, maintaining focal adhesion and cell viability.
  • Targeting NADPH oxidase may represent a therapeutic strategy for melanoma treatment.

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