[Cancer Malignancy by Abnormal Claudin Expression]

An elevated expression of claudins(CLDNs), tight junctional proteins, are reported in various solid tumors. However, the expression mechanisms and pathophysiological roles of CLDNs have not been well clarified. So far, we found that CLDN2 and CLDN14 are highly expressed in lung adenocarcinoma and colorectal cancer cells, respectively. These CLDNs augmented proliferation of cancer cells. Furthermore, these CLDNs enhanced chemoresistance of cancer spheroids mediated by the elevation of oxidative stress and activation of Nrf2 signal pathway. The restriction of glucose supply, shift of glucose metabolism from aerobic glycolysis towards oxidative phosphorylation, and elevation of mitochondria activity were suggested to be involved in the CLDN2-dependent activation of Nrf2 signal pathway. The CLDN expression inhibitors are expected to have functions of proliferation inhibition and anticancer drug resistance improvement effects. We have to search for the optimal CLDN subtype as therapeutic target because the expression pattern of CLDN subtypes is different in the type of cancer.