The Expression of CLDN6 in Hepatocellular Carcinoma Tissue and the Effects of CLDN6 on Biological Phenotypes of Hepatocellular Carcinoma Cells

Abstract

CLDN6, a member of claudin (CLDN) family, was found to be a breast cancer suppressor gene in our early experiments. However, CLDN6 was highly expressed in human hepatocellular carcinoma (hHCC) (TCGA database), and the role of CLDN6 in hHCC is still unclear. To investigate the expression of CLDN6, immunohistochemical staining was performed in hHCC tissues. As a result, hHCC tissues highly expressed CLDN6, and the expression was related to the degree of tumor's differentiation. To research the role of CLDN6 in hHCC cells, CLDN6 was silenced in HepG2 and Hep3B cells which highly expressed CLDN6 through liposome transfection. Results showed that after silencing of CLDN6, the proliferation, migration and invasion abilities of hHCC cells were inhibited. Meanwhile, the expression of E-cadherin was upregulated, and the expression of N-cadherin and Vimentin was downregulated. All the results above indicated that CLDN6 promoted the development of hHCC, and could be a potential target for the treatment of it.

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

“…Notably, CLDN6 exerts carcinogenic or anti–carcinogenic effects depending on the tissue or cell type [ 27 ]. As for proliferation, CLDN6 promotes cell proliferation in human hepatocellular carcinoma, gastric cancer, and endometrial carcinoma [ 28 , 29 , 30 , 31 ]. However, we have found the proliferation of MCF–7 breast cancer cells was suppressed upon CLDN6 overexpression, but the mechanism was unknown.…”

CLDN6: From Traditional Barrier Function to Emerging Roles in Cancers

“…The comparison revealed that the expression of CLDN6 in the same tumor may not be identical or even contradictory in different studies. For example, Tetsuo Ushiku et al [49] found a positive rate of 0% for CLDN6, while Yan Lu et al [50] found a positive expression rate of 79.2% in hepatocellular carcinoma. This may be related to intratumor heterogeneity, the number of cases, different experimental methods, or different manufacturers of antibodies, and further validation is needed as to whether CLDN6 can be a biomarker for identifying certain tumors.…”

“…Studies have shown that CLDN6 inhibits the development and progression in some cancers such as breast cancer [22,24,[61][62][63], cervical cancer [56], and meningioma [64]. In hepatocellular cancer [50,65,66], gastric cancer [52,67], endometrial cancer [68,69], and ovarian cancer [70], CLDN6 has the opposite roles. The oncogenic role or conversely tumor-suppressive effect of CLDN6 in different types of cancer is shown in Table 2.…”

“…Similarly, CLDN6 overexpression in cervical carcinoma cells inhibits tumor growth in vitro and in vivo [56]. However, CLDN6 promotes the proliferation of human hepatocellular carcinoma cells [50,65]. CLDN6 also acts as a tumor promoter to increase cell proliferation in gastric cancer [52].…”

“…In gastric cancer cells, CLDN6 interacted with LATS1/2 to reduce the phosphorylation of YAP, resulting in the level of YAP increasing in the nucleus, which interacts with snail1 to bind to the promoter of EMT related genes to enhance the migration and invasion abilities [52]. CLDN6 silencing inhibits the migration and invasion abilities of HCC cells, which may be dependent on its repression of EMT [50].…”