In addition, the expression of NOX3 and NOX4 was significantly up-regulated, which affected the generation of ROS and associated with the metastasis of breast cancer.
Here, we report a molecular axis, comprising the molecular adaptor hydrogen peroxide-inducible clone-5 (HIC-5), NADPH oxidase 4 (NOX4), and mitochondria-associated reactive oxygen species (mtROS), that regulates MMP9 expression and may be a target to suppress cancer metastasis.
The univariate and multivariable analyses showed that negative nodal metastasis and low expression of Nox4 were significantly associated with superior disease-free survival (DFS) and overall survival (OS).
Our studies provide new insight into TGFβ/SMAD3 and mut-p53-mediated NOX4 induction involving epigenetic control of NOX4 in tumor cell migration, suggesting NOX4 is a potential therapeutic target to combat tumor progression and metastasis.
Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood.
We propose that inhibition of Nox4 (which is known to be strongly expressed in many tumors) could be studied as a new target for cancer treatment, in particular for inhibition of metastasis.