Table 1 Invasion-related traits associated with NOXs expression and function
From: NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion
NOX protein | Cancer type | Associated characteristic | Reference |
|---|---|---|---|
NOX1 | Colon cancer | NF-kB promotes the expression of NOX1 and ROS levels, thereby promoting the adhesive capacity of tumor cells | [57] |
Gallbladder cancer | Increased NOX1 expression in cancer-associated fibroblasts correlates with increased cellular invasiveness and poor prognosis | [59] | |
Colon Cancer | NOX1 contributes to the formation of invadopodia through the production of ROS. Its activation is dependent on the phosphorylation of NoxA1, Tks4, and Tks5 mediated by c-Src | ||
NOX2 | Colon Cancer | Elevated levels of ROS, dependent on increased expression of NOX2, downregulate the MAPK signaling pathway, leading to an upregulation in MMP7 production | [58] |
Gastric cancer | Increased expression of NOX2 is related to an increase in the invasiveness of tumor cells | [60] | |
Cervical cancer | TGF-β1 induces the upregulation of NOX2, leading to increased expression of EMT markers | [63] | |
Urothelial carcinoma | TGIF induces an increase in phosphorylation of PI3K/AKT, leading to an increase in NOX2-dependent ROS levels, thereby enhancing the invasiveness of tumor cells | [65] | |
NOX4 | Kidney cancer | Under hypoxic conditions, a negative regulation of MAPK is generated, which is associated with increased NOX4 activity, promoting invasion through the secretion of IL-6 and IL-8 | [61] |
Gastric Cancer | Overexpression of NOX4 associated with positive regulation in MMP7 production and increased invasiveness | [62] | |
Cervical cancer | TGF-β1 induces the upregulation of NOX4, leading to increased expression of EMT markers | [63] | |
Lung cancer | TGF-β positively regulates NOX4 expression through NF-κB activation, inducing an increase in ROS levels, thereby regulating the expression of EMT markers such as Vimentin and Snail, while decreasing the expression of E-cadherin | [64] | |
Glioblastoma | TGF-β1 induces up-regulation of mRNA and protein levels of NOX4, leading to increased production of ROS. This activation subsequently triggers the PI3K/AKT/HIF-1α axis, resulting in increased expression of EMT markers such as Vimentin and N-cadherin | [66] | |
NOX5 | Colon cancer | Associated with increased motility because it regulates integrin-linked kinase signaling pathways | [51] |
Breast cancer | NOX5 expression modulated by STAT5A, and NOX5 depletion decreases invasiveness | [52] | |
Prostate cancer | Increased levels of ROS by NOX5 induces activation of HIF1α and levels of MMP14, increasing the invasiveness and proteolytic capacity of tumor cells | ||
DUOX1 | Lung cancer | Induced increase of molecular marker associated to EMT through silencing of DUOX1 | [49] |
DUOX2 | Colon cancer | Increased DUOX2-dependent ROS induces the expression of molecular markers associated with EMT | [50] |