NADPH Oxidases: Insights into Selected Functions and Mechanisms of Action in Cancer and Stem Cells

Figure 3

Examples of NOX signal transduction. NOX1-derived ROS can affect the following: differentiation through the p38 and ERK1/2 pathway, hypertrophy via p38-mediated activation of Akt, cell migration by the activation of cSrc protein, and cellular growth by the activation of ERK1/2; and subsequent activation of transcription factor Ets-1 and upregulation of cyclin D. nox1 also downregulates the expression and activity of the antiangiogenic receptor PPARα, known to inhibit the transcription factor NF-κB and, therefore, affects angiogenesis. NOX1 can be activated by thrombin, PDGF, or Ang II; activated by TNFα, thrombin or NF-κB NOX2-generated ROS promote migration and angiogenesis through the Akt and cSrc pathways. NOX2-mediated regulation of angiogenesis also occurs via VE-cadherin; via the activation of p38 or the inhibition of ERK1/2 NOX4-derived ROS promotion; via the activation of p38 or the inhibition of ERK1/2 differentiation, which regulates growth, by eiF4E and pRB pathways, and migration (through the activation of MMP2). NOX4 expression and activity can be increased by TGF-β1 or Ang II; NOX5 promotes growth and inflammation, respectively, through JAK-2/STAT3 and NF-κB signaling pathways. ROS production by NOX5 can be activated by IL4 or PDGF; there will be always some omitted proteins, no matter how detailed is the scheme.