ArticleJournal of experimental & clinical cancer research : CR2017
CLDN6 promotes chemoresistance through GSTP1 in human breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 69 citations in OpenAlex.
- Unveiling the Role of GlutathioneACS pharmacology & translational science · 2026Review
- Anti-cancer effects of carvacrol on NUF2, CASP3 and CLDN6 expression in T47D breast cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Multiomics analysis of GSTP1 knockdown pancreatic cancer cells reveals key regulators of redox and metabolic homeostasis.Biology open · 2025Article
- A Mutual Interaction Between GSTP1 and p53 Improves the Drug Resistance and Malignant Biology of Pancreatic Cancer.Cancer science · 2025Article
- CLDN6 induces chemoresistance through protective autophagy in breast cancer.International journal of biological sciences · 2025Article
- ESR1 Fusions Invoke Breast Cancer Subtype-Dependent Enrichment of Ligand-Independent Oncogenic Signatures and Phenotypes.Endocrinology · 2024Article
- CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation.Cellular & molecular biology letters · 2024Article
- Independent prognostic value of CLDN6 in bladder cancer based on M2 macrophages related signature.iScience · 2024Article
- Claudins: from gatekeepers of epithelial integrity to potential targets in hepato-pancreato-biliary cancers.Frontiers in oncology · 2024Review
- Transcriptome-wide analysis of the differences between MCF7 cells cultured in DMEM or αMEM.PloS one · 2024Article
- Antibody-mediated targeting of Claudins in cancer.Frontiers in oncology · 2024Review
- Expression of Claudin-9 (CLDN9) in Breast Cancer, the Clinical Significance in Connection with Its Subcoat Anchorage Proteins ZO-1 and ZO-3 and Impact on Drug Resistance.Biomedicines · 2023Article
- Expression patterns of claudins in cancer.Heliyon · 2023Review
- Advances in drug resistance of triple negative breast cancer caused by pregnane X receptor.World journal of clinical oncology · 2023Review
- Binding of YY1/CREB to an Enhancer Region Triggers Claudin 6 Expression inInternational journal of molecular sciences · 2023Article
- A GSTP1-mediated lactic acid signaling promotes tumorigenesis through the PPP oxidative branch.Cell death & disease · 2023Article
- Role of p53 suppression in the pathogenesis of hepatocellular carcinoma.World journal of gastrointestinal pathophysiology · 2023Review
- p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act.Nutrients · 2023Review
- Therapeutic Effects of WT1 Silencing via Respiratory Administration of Neutral DOPC Liposomal-siRNA in a Lung Metastasis Melanoma Murine Model.Non-coding RNA · 2023Article
- CLDN6 inhibits breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy.Journal of experimental & clinical cancer research : CR · 2023Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClaudin-6 (CLDN6), a member of CLDN family and a key component of tight junction, has been reported to function as a tumor suppressor in breast cancer. However, whether CLDN6 plays any role in breast cancer chemoresistance remains unclear. In this study, we investigated the role of CLDN6 in the acquisition of chemoresistance in breast cancer cells.
methodsWe manipulated the expression of CLDN6 in MCF-7 and MCF-7/MDR cells with lv-CLDN6 and CLDN6-shRNA and investigated whether CLDN6 manipulation lead to different susceptibilities to several chemotherapeutic agents in these cells. The cytotoxicity of adriamycin (ADM), 5-fluorouracil (5-FU), and cisplatin (DDP) was tested by cck-8 assay. Cell death was determined by DAPI nuclear staining. The enzyme activity of glutanthione S-transferase-p1 (GSTP1) was detected by a GST activity kit. Then lv-GSTP1 and GSTP1-shRNA plasmids were constructed to investigate the potential of GSTP1 in regulating chemoresistance of breast cancer. The TP53-shRNA was adopted to explore the regulation mechanism of GSTP1. Finally, immunohistochemistry was used to explore the relationship between CLDN6 and GSTP1 expression in breast cancer tissues.
resultsSilencing CLDN6 increased the cytotoxicity of ADM, 5-FU, and DDP in MCF-7/MDR cells. Whereas overexpression of CLDN6 in MCF-7, the parental cell line of MCF-7/MDR expressing low level of CLDN6, increased the resistance to the above drugs. GSTP1 was upregulated in CLDN6-overexpressed MCF-7 cells. RNAi -mediated silencing of CLDN6 downregulated both GSTP1 expression and GST enzyme activity in MCF-7/MDR cells. Overexpresssion of GSTP1 in CLDN6 silenced MCF-7/MDR cells restored chemoresistance, whereas silencing GSTP1 reduced the chemoresistance due to ectopic overexpressed of CLDN6 in MCF-7 cells. These observations were also repeated in TNBC cells Hs578t. We further confirmed that CLDN6 interacted with p53 and promoted translocation of p53 from nucleus to cytoplasm, and both the expression and enzyme activity of GSTP1 were regulated by p53. Clinicopathologic analysis revealed that GSTP1 expression was positively associated with CLDN6 in human breast cancer samples.
conclusionHigh expression of CLDN6 confers chemoresistance on breast cancer which is mediated by GSTP1, the activity of which is regulated by p53. Our findings provide a new insight into mechanisms and strategies to overcome chemoresistance in breast cancer.
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