ArticleJournal of experimental & clinical cancer research : CR2023
CLDN6 inhibits breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Review
- Article
- High expression of the ADC target Claudin-6 associates with aggressive endometrial cancer and remains high in metastatic lesions.BJC reports · 2026Article
- Review
- Anti-cancer effects of carvacrol on NUF2, CASP3 and CLDN6 expression in T47D breast cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Involvement of claudins 6 and 9 in epithelial-mesenchymal transition and the metastatic process.Tissue barriers · 2026Review
- The Role of Actin-Binding Proteins in Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2026Review
- Electroacupuncture alleviates functional dyspepsia by modulating the vagus nerve to regulate duodenal microbiota and suppress TWEAK/Fn14/NF-κB and arachidonic acid metabolic pathways.Frontiers in immunology · 2026Article
- Hypomethylation induced overexpression of PLOD3 facilitates colorectal cancer progression through TM9SF4-mediated autophagy.Cell death & disease · 2025Article
- Multifaceted role of the actin-binding protein WIP: Promotor and inhibitor of tumor progression and dissemination.Cytoskeleton (Hoboken, N.J.) · 2025Review
- CLDN6 triggers NRF2-mediated ferroptosis through recruiting DLG1/PBK complex in breast cancer.Cell death & disease · 2025Article
- USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer.Cell death & disease · 2025Article
- CLDN6 induces chemoresistance through protective autophagy in breast cancer.International journal of biological sciences · 2025Article
- The role of autophagy in cancer: from molecular mechanism to therapeutic window.Frontiers in immunology · 2025Review
- Mycobacterial antigen Ag85B restrains Hodgkin lymphoma tumor growth by inhibiting autophagy.Oncology research · 2025Article
- Early death prediction model for breast cancer with synchronous lung metastases: an analysis of the SEER database.Gland surgery · 2024Article
- B3GALT4 modulates tumor progression and autophagy by AKT/mTOR signaling pathway in breast cancer.Discover oncology · 2024Article
- CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation.Cellular & molecular biology letters · 2024Article
- Claudins in Cancer: A Current and Future Therapeutic Target.International journal of molecular sciences · 2024Review
- NPFs-mediated actin cytoskeleton: a new viewpoint on autophagy regulation.Cell communication and signaling : CCS · 2024Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAs a breast cancer suppressor gene, CLDN6 overexpression was found to inhibit breast cancer metastasis in our previous studies, but the specific mechanism remains unclear. This study aimed to clarify the role and mechanism of CLDN6 in inhibiting breast cancer metastasis.
methodsWestern blot, immunofluorescence and transmission electron microscopy were performed to detect autophagy. Wound healing, transwell assays and lung metastasis mouse models were used to examine breast cancer metastasis. Phalloidin staining and immunofluorescent staining were used to observe actin cytoskeleton. mRNA seq, RT-PCR, western blot, chromatin immunoprecipitation, dual luciferase reporter assay, co-immunoprecipitation and immunofluorescence were performed to define the molecular mechanism. The expression levels and clinical implication of CLDN6, WIP and LC3 in breast cancer tissues were evaluated using immunohistochemistry.
resultsWe demonstrated that CLDN6 inhibited breast cancer metastasis through autophagy in vitro and vivo. We unraveled a novel mechanism that CLDN6 regulated autophagy via WIP-dependent actin cytoskeleton assembly. Through its PDZ-binding motif, overexpressed CLDN6 interacted with JNK and upregulated JNK/c-Jun pathway. C-Jun promoted WIP expression at the transcriptional level. Notably, we observed c-Jun transcriptionally upregulated CLDN6 expression, and there was a positive feedback loop between CLDN6 and JNK/c-Jun. 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.
conclusionsThe 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. Our findings enrich the theoretical basis for CLDN6 as a potential biomarker for breast cancer diagnosis and therapy.
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