Tight junction protein claudin-6 inhibits growth and induces the apoptosis of cervical carcinoma cells in vitro and in vivo

Zhang, Xiaowei; Ruan, Yuanyuan; Li, Yanru; Lin, Dongjing; Quan, Chengshi

doi:10.1007/s12032-015-0600-4

Cited by 29 publications

(31 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Stress induced apoptosis worked through activation of the ASK1-p38 MAPK pathway (35)(36)(37). Several studied have shown that CLDNs induce apoptosis of cancer cells such as cervical carcinoma and breast cancer cells (17,(38)(39)(40). Our data showed that CLDN6 significantly inhibited MCF-7 cell apoptosis with TRX1 treatment.…”

Section: Discussionsupporting

confidence: 50%

“…Accumulating evidence suggests that CLDNs induce tumor apoptosis through activating MAPK signal pathway, such as CLDN6 induces tumor apoptosis through activating the ERK1/2 signaling pathway (17), and CLDN7 promotes apoptosis through the activation of p38 protein kinase in MKN28 gastric epithelial cells (18). The present study dissects the molecular mechanisms by which CLDN6 induced apoptosis in MCF-7 breast cancer cells.…”

Section: Introductionmentioning

confidence: 72%

See 1 more Smart Citation

CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells

Guo

Lin

Zhang

et al. 2016

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

Claudin 6 (CLDN6), a member of tight junction protein claudin (CLDN) family, inhibits proliferation and induces apoptosis of MCF-7 breast cancer cells. However, these molecular mechanisms of CLDN6-induced apoptosis remain largely elusive. We previously found that restoration of human CLDN6 gene expression was correlated with the expression level of apoptosis signal-regulating kinase 1 (ASK1) using cDNA array and bioinformatics analysis. ASK1, a mitogen-activated protein kinase kinase kinase, is involved in environmental stress-activation of the c-jun N-terminal kinase (JNK) and p38 pathways, which contribute to apoptosis-associated tumor cell death. In the present study, we show that the restoration of CLDN6 gene expression in MCF-7 cells marhedly decreased ASK1 phosphorylation at Ser967. Activated ASK1ser967 further induced the activation of downstream targets, JNK and p38 kinase. MCF-7/CLDN6 stable transfection cell clone treated with TRX1, an ASK1 inhibitor, showed suppressed JNK and p38 activation, and showed substantially increased survival and colony formation and reduced percent of apoptotic cells using TUNEL staining and DNA ladder. Furthermore, TRX1 treatment increased Bcl-2/Bax ratio and reduced caspase-3 cleavage in MCF-7/CLDN6 stable transfection cell clone. Therefore, these data show that CLDN6 mediates ASK1-p38/JNK apoptotic signaling in MCF-7 cells, and it is correlated with constitutive deregulation of the balance of Bcl-2 family proteins and activation of caspase-3.

show abstract

Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 72%

CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells

Guo

Lin

Zhang

et al. 2016

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Zhu et al noticed that the expression of claudin-5 and claudin-9 is downregulated in cervical carcinoma tissues compared with adjacent non-neoplastic tissues, while claudin-8 is elevated [74]. In contrast to claudin-1, claudin-6 is downregulated in cervical carcinoma, and expression of claudin-6 leads to decreased cell proliferation, colony formation in vitro, and tumor growth in vivo [116]. Based on this observation, it was suggested that this protein may be a tumor suppressor for cervical cancer.…”

Section: Claudins In Cervical Cancermentioning

confidence: 99%

Claudins: New Players in Human Fertility and Reproductive System Cancers

Kozieł

Kowalska

Piastowska-Ciesielska

2020

Cancers

View full text Add to dashboard Cite

Claudins are major integral proteins of tight junctions (TJs), the apical cell-cell adhesions that enable maintaining polarity of epithelial cells, their differentiation, and cell signaling. A number of studies have indicated that claudins might play a crucial role in both physiology and pathogenesis. Their tissue-specific expression was originally linked to the development of different types of cancer and triggered a hope to use them as diagnostic or prognostic markers. However, it seems that their expression is more complex than that, and undoubtedly, claudins participate in one of the most important molecular events in cells. This review summarizes the recent research evaluating the role of claudins in fertility and the most common endocrine-dependent cancers in the reproductive system and highlights the crucial role of claudins both in human fertility and the most common cancers.

show abstract

“…A cell immunofluorescence assay was conducted as previously described. 24 In brief, after washing three times with PBS and fixed with 4% paraformaldehyde for 10 min at RT, the cells were permeabilized with 0.…”

Section: Immunofluorescence Methodsmentioning

confidence: 99%

“…The 4-μm thick sections were deparaffinized in xylene, rehydrated through a graded ethanol, series and coated in 3% hydrogen peroxide for 10 min at room temperature (RT) in order to block endogenous peroxidase activity, according to the protocol outlined in a previous study. 24 The sections were then stained with an anti-CLDN12 at a 1:350 dilution (cat. no.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

<p>The Cytoplasmic Expression Of CLDN12 Predicts An Unfavorable Prognosis And Promotes Proliferation And Migration Of Osteosarcoma</p>

Tian¹,

He²,

Han³

et al. 2019

CMAR

View full text Add to dashboard Cite

Background: To date, the impact and potential molecular mechanisms of CLDN12 and its association with malignancy in osteosarcoma have not been determined. Materials and methods: In the present study, the expression profiles of CLDN12 in osteosarcoma cell lines and tissues were explored by immunohistochemistry. A fetal osteoblast cell line was transfected with a eukaryotic expression plasmid, and endogenous CLDN12 in osteosarcoma cells were silenced through an RNA interference (RNAi) method. These transfections were verified, and the activation state of Thr308 site in protein kinase B (Akt) was explored by Western blotting. Moreover, the malignant phenotype of osteosarcoma cells was evaluated by cell counting kit-8 (CCK-8), colony formation, Transwell, and wound-healing assays. Furthermore, osteoblast cells were treated with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 to determine the impact of the PI3K/Akt signaling pathway on cell migration ability. Results: The results revealed that CLDN12 was overexpressed and localized in the cytoplasm of osteosarcoma cells, and its overexpression was associated with an unfavorable prognosis, irrespective of tumor node metastasis stage. In addition, the knockdown of CLDN12 in cultured osteosarcoma cells markedly attenuated cell proliferation and migration, as indicated by the Cell Counting Kit-8 assay, colony formation assay, scratch wound healing assay and Transwell migration assay. The results also demonstrated that the overexpression of CLDN12 increased the activation of Thr308 site in Akt in fetal osteoblast cells, and the PI3K inhibitor LY294002 partially decreased CLDN12-promoted proliferation and metastasis. Conclusion: In conclusion, the results of the present study indicated that CLDN12 promoted cell proliferation and migration through the PI3K/Akt signaling pathway in osteosarcoma cells, suggesting that CLDN12 may be a potential agent in the treatment of patients with osteosarcoma.

show abstract

Tight junction protein claudin-6 inhibits growth and induces the apoptosis of cervical carcinoma cells in vitro and in vivo

Cited by 29 publications

References 35 publications

CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells

CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells

Claudins: New Players in Human Fertility and Reproductive System Cancers

<p>The Cytoplasmic Expression Of CLDN12 Predicts An Unfavorable Prognosis And Promotes Proliferation And Migration Of Osteosarcoma</p>

Contact Info

Product

Resources

About