Another open question is why some studies found that depletion of NOX4 expression alone, either by shRNA techniques in vitro or in NOX4-/- mice, was able to impact fibroblast activation in other tumour types, such as prostate,45 oesophageal15 or breast cancers.46 Perhaps the levels and/or function of NOX1 or the components of its regulatory complex (i.e. p22phox) are different in these organs and insufficient to trigger a compensatory mechanism after NOX4 depletion. Here, NOX1 is linked to neoplasm.