![]() ![]() Previously, we have cloned CLDN6 as a candidate suppressor gene of breast cancer from COP rat mammary epithelial cells for the first time. ![]() In addition to traditional functions of CLDN6 in permeability regulation and barrier formation, CLDN6 connects proteins containing PDZ domain or PBM through its PBM, regulating intracellular signaling pathways to affect the malignant phenotype of cancer. CLDN6 is a member of the CLDNs family, containing four transmembrane helices and a COOH-terminal PDZ-binding motif (PBM). Our findings enrich the theoretical basis for CLDN6 as a potential biomarker for breast cancer diagnosis and therapy.ĬLDNs are the main components of tight junctions of epithelial cells. The data provide a new insight into the inhibitory effects of CLDN6-mediated autophagy on breast cancer metastasis, and revealed the new mechanism of CLDN6 regulating autophagy through WIP-dependent actin cytoskeleton. Finally, we found that CLDN6, WIP and LC3 expression correlated with each other, and WIP expression was significantly associated with lymph node metastasis of breast cancer patients. Notably, we observed c-Jun transcriptionally upregulated CLDN6 expression, and there was a positive feedback loop between CLDN6 and JNK/c-Jun. C-Jun promoted WIP expression at the transcriptional level. Through its PDZ-binding motif, overexpressed CLDN6 interacted with JNK and upregulated JNK/c-Jun pathway. We unraveled a novel mechanism that CLDN6 regulated autophagy via WIP-dependent actin cytoskeleton assembly. We demonstrated that CLDN6 inhibited breast cancer metastasis through autophagy in vitro and vivo. The expression levels and clinical implication of CLDN6, WIP and LC3 in breast cancer tissues were evaluated using immunohistochemistry. mRNA seq, RT-PCR, western blot, chromatin immunoprecipitation, dual luciferase reporter assay, co-immunoprecipitation and immunofluorescence were performed to define the molecular mechanism. Phalloidin staining and immunofluorescent staining were used to observe actin cytoskeleton. Wound healing, transwell assays and lung metastasis mouse models were used to examine breast cancer metastasis. Western blot, immunofluorescence and transmission electron microscopy were performed to detect autophagy. This study aimed to clarify the role and mechanism of CLDN6 in inhibiting breast cancer metastasis. Note that in the agile board above, the team has too many code reviews, so the column has turned red to indicate that.As a breast cancer suppressor gene, CLDN6 overexpression was found to inhibit breast cancer metastasis in our previous studies, but the specific mechanism remains unclear. WIP limits guarantee un-reviewed code doesn't pile up.
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