Claudin 6: Therapeutic prospects for tumours, and mechanisms of expression and regulation (Review)
- Authors:
- Huan Du
- Xiyue Yang
- Jinjia Fan
- Xiaobo Du
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Affiliations: Department of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China - Published online on: July 23, 2021 https://doi.org/10.3892/mmr.2021.12316
- Article Number: 677
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Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
Li J, Ananthapanyasut W and Yu AS: Claudins in renal physiology and disease. Pediatr Nephrol. 26:2133–2142. 2011. View Article : Google Scholar : PubMed/NCBI | |
Singh AB, Uppada SB and Dhawan P: Claudin proteins, outside-in signaling, and carcinogenesis. Pflugers Arch. 469:69–75. 2017. View Article : Google Scholar : PubMed/NCBI | |
Hu CA, Hou Y, Yi D, Qiu Y, Wu G, Kong X and Yin Y: Autophagy and tight junction proteins in the intestine and intestinal diseases. Anim Nutr. 1:123–127. 2015. View Article : Google Scholar : PubMed/NCBI | |
English DP and Santin AD: Claudins overexpression in ovarian cancer: Potential targets for clostridium perfringens enterotoxin (CPE) based diagnosis and therapy. Int J Mol Sci. 14:10412–10437. 2013. View Article : Google Scholar : PubMed/NCBI | |
Tabariès S and Siegel PM: The role of claudins in cancer metastasis. Oncogene. 36:1176–1190. 2017. View Article : Google Scholar : PubMed/NCBI | |
Ushiku T, Shinozaki-Ushiku A, Maeda D, Morita S and Fukayama M: Distinct expression pattern of claudin-6, a primitive phenotypic tight junction molecule, in germ cell tumours and visceral carcinomas. Histopathology. 61:1043–1056. 2012. View Article : Google Scholar : PubMed/NCBI | |
Gowrikumar S, Singh AB and Dhawan P: Role of claudin proteins in regulating cancer stem cells and chemoresistance-potential implication in disease prognosis and therapy. Int J Mol Sci. 21:532019. View Article : Google Scholar : PubMed/NCBI | |
Kwon MJ: Emerging roles of claudins in human cancer. Int J Mol Sci. 14:18148–18180. 2013. View Article : Google Scholar : PubMed/NCBI | |
Singh AB and Dhawan P: Claudins and cancer: Fall of the soldiers entrusted to protect the gate and keep the barrier intact. Semin Cell Dev Biol. 42:58–65. 2015. View Article : Google Scholar : PubMed/NCBI | |
Chen S, Liu X and Luo W: Advances in the application of claudins to tumor therapy. Sheng Wu Gong Cheng Xue Bao. 35:931–941. 2019.(In Chinese). PubMed/NCBI | |
Reinhard K, Rengstl B, Oehm P, Michel K, Billmeier A, Hayduk N, Klein O, Kuna K, Ouchan Y, Wöll S, et al: An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors. Science. 367:446–453. 2020. View Article : Google Scholar : PubMed/NCBI | |
Singh AB, Sharma A and Dhawan P: Claudin family of proteins and cancer: An overview. J Oncol. 2010:5419572010. View Article : Google Scholar : PubMed/NCBI | |
Lin D, Guo Y, Li Y, Ruan Y, Zhang M, Jin X, Yang M, Lu Y, Song P, Zhao S, et al: Bioinformatic analysis reveals potential properties of human claudin-6 regulation and functions. Oncol Rep. 38:875–885. 2017. View Article : Google Scholar : PubMed/NCBI | |
Anderson WJ, Zhou Q, Alcalde V, Kaneko OF, Blank LJ, Sherwood RI, Guseh JS, Rajagopal J and Melton DA: Genetic targeting of the endoderm with claudin-6CreER. Dev Dyn. 237:504–512. 2008. View Article : Google Scholar : PubMed/NCBI | |
Sugimoto K, Ichikawa-Tomikawa N, Kashiwagi K, Endo C, Tanaka S, Sawada N, Watabe T, Higashi T and Chiba H: Cell adhesion signals regulate the nuclear receptor activity. Proc Natl Acad Sci USA. 116:24600–24609. 2019. View Article : Google Scholar : PubMed/NCBI | |
Hoevel T, Macek R, Swisshelm K and Kubbies M: Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids. Int J Cancer. 108:374–383. 2004. View Article : Google Scholar : PubMed/NCBI | |
Yafang L, Qiong W, Yue R, Xiaoming X, Lina Y, Mingzi Z, Ting Z, Yulin L and Chengshi Q: Role of estrogen receptor-α in the regulation of claudin-6 expression in breast cancer cells. J Breast Cancer. 14:20–27. 2011. View Article : Google Scholar : PubMed/NCBI | |
Mullin JM: Potential interplay between luminal growth factors and increased tight junction permeability in epithelial carcinogenesis. J Exp Zool. 279:484–489. 1997. View Article : Google Scholar : PubMed/NCBI | |
Stadler CR, Bähr-Mahmud H, Plum LM, Schmoldt K, Kölsch AC, Türeci Ö and Sahin U: Characterization of the first-in-class T-cell-engaging bispecific single-chain antibody for targeted immunotherapy of solid tumors expressing the oncofetal protein claudin 6. Oncoimmunology. 5:e10915552015. View Article : Google Scholar : PubMed/NCBI | |
Ben-David U, Nudel N and Benvenisty N: Immunologic and chemical targeting of the tight-junction protein claudin-6 eliminates tumorigenic human pluripotent stem cells. Nat Commun. 4:19922013. View Article : Google Scholar : PubMed/NCBI | |
Wu Q, Liu Y, Ren Y, Xu X, Yu L, Li Y and Quan C: Tight junction protein, claudin-6, downregulates the malignant phenotype of breast carcinoma. Eur J Cancer Prev. 19:186–194. 2010. View Article : Google Scholar : PubMed/NCBI | |
Jia H, Chai X, Li S, Wu D and Fan Z: Identification of claudin-2, −6, −11 and −14 as prognostic markers in human breast carcinoma. Int J Clin Exp Pathol. 12:2195–2204. 2019.PubMed/NCBI | |
Wu Q, Liu YF, Ren Y, Xu XM, Yu LN, Li YL and Quan CS: Effects of stable up-regulation of tight junction protein claudin-6 upon biological phenotypes of breast cancer cell MCF-7. Zhonghua Yi Xue Za Zhi. 90:407–412. 2010.(In Chinese). PubMed/NCBI | |
Heerma van Voss MR, van Diest PJ, Smolders YH, Bart J, van der Wall E and van der Groep P: Distinct claudin expression characterizes BRCA1-related breast cancer. Histopathology. 65:814–827. 2014. View Article : Google Scholar : PubMed/NCBI | |
Xu X, Jin H, Liu Y, Liu L, Wu Q, Guo Y, Yu L, Liu Z, Zhang T, Zhang X, et al: The expression patterns and correlations of claudin-6, methy-CpG binding protein 2, DNA methyltransferase 1, histone deacetylase 1, acetyl-histone H3 and acetyl-histone H4 and their clinicopathological significance in breast invasive ductal carcinomas. Diagn Pathol. 7:332012. View Article : Google Scholar : PubMed/NCBI | |
Lu Y, Wang L, Li H, Li Y, Ruan Y, Lin D, Yang M, Jin X, Guo Y, Zhang X and Quan C: SMAD2 inactivation inhibits CLDN6 methylation to suppress migration and invasion of breast cancer cells. Int J Mol Sci. 18:18632017. View Article : Google Scholar : PubMed/NCBI | |
Li Q, Zhu F and Chen P: miR-7 and miR-218 epigenetically control tumor suppressor genes RASSF1A and claudin-6 by targeting HoxB3 in breast cancer. Biochem Biophys Res Commun. 424:28–33. 2012. View Article : Google Scholar : PubMed/NCBI | |
Liu Y, Jin X, Li Y, Ruan Y, Lu Y, Yang M, Lin D, Song P, Guo Y, Zhao S, et al: DNA methylation of claudin-6 promotes breast cancer cell migration and invasion by recruiting MeCP2 and deacetylating H3Ac and H4Ac. J Exp Clin Cancer Res. 35:1202016. View Article : Google Scholar : PubMed/NCBI | |
Ren Y, Wu Q, Liu Y, Xu X and Quan C: Gene silencing of claudin-6 enhances cell proliferation and migration accompanied with increased MMP-2 activity via p38 MAPK signaling pathway in human breast epithelium cell line HBL 100. Mol Med Rep. 8:1505–1510. 2013. View Article : Google Scholar : PubMed/NCBI | |
Jia Y, Guo Y, Jin Q, Qu H, Qi D, Song P, Zhang X, Wang X, Xu W, Dong Y, et al: A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis. J Exp Clin Cancer Res. 39:422020. View Article : Google Scholar : PubMed/NCBI | |
Guo Y, Xu X, Liu Z, Zhang T, Zhang X, Wang L, Wang M, Liu Y, Lu Y, Liu Y and Quan C: Apoptosis signal-regulating kinase 1 is associated with the effect of claudin-6 in breast cancer. Diagn Pathol. 7:1112012. View Article : Google Scholar : PubMed/NCBI | |
Guo Y, Lin D, Zhang M, Zhang X, Li Y, Yang R, Lu Y, Jin X, Yang M, Wang M, et al: CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells. Int J Oncol. 48:2435–2444. 2016. View Article : Google Scholar : PubMed/NCBI | |
Song P, Li Y, Dong Y, Liang Y, Qu H, Qi D, Lu Y, Jin X, Guo Y, Jia Y, et al: Estrogen receptor β inhibits breast cancer cells migration and invasion through CLDN6-mediated autophagy. J Exp Clin Cancer Res. 38:3542019. View Article : Google Scholar : PubMed/NCBI | |
Figueiredo NB, Cestari SH, Conde SJ, Luvizotto RA, De Sibio MT, Perone D, Katayama ML, Carraro DM, Brentani HP, Brentani MM and Nogueira CR: Estrogen-responsive genes overlap with triiodothyronine-responsive genes in a breast carcinoma cell line. ScientificWorldJournal. 2014:9694042014. View Article : Google Scholar : PubMed/NCBIPubMed/NCBIPubMed/NCBI | |
Wu Q, Liu X, Liu YF, Lu Y, Wang LP, Zhang XW, Li YL and Quan CS: Inhibition of p38 activity reverses claudin-6 induced cell apoptosis, invasion, and migration. Chin Med J (Engl). 126:3539–3544. 2013.PubMed/NCBI | |
Lin Z, Zhang X, Liu Z, Liu Q, Wang L, Lu Y, Liu Y, Wang M, Yang M, Jin X and Quan C: The distinct expression patterns of claudin-2, −6, and −11 between human gastric neoplasms and adjacent non-neoplastic tissues. Diagn Pathol. 8:1332013. View Article : Google Scholar : PubMed/NCBI | |
Zavala-Zendejas VE, Torres-Martinez AC, Salas-Morales B, Fortoul TI, Montaño LF and Rendon-Huerta EP: Claudin-6, 7, or 9 overexpression in the human gastric adenocarcinoma cell line AGS increases its invasiveness, migration, and proliferation rate. Cancer Invest. 29:1–11. 2011. View Article : Google Scholar : PubMed/NCBI | |
Kohmoto T, Masuda K, Shoda K, Takahashi R, Ujiro S, Tange S, Ichikawa D, Otsuji E and Imoto I: Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer. Gastric Cancer. 23:403–417. 2020. View Article : Google Scholar : PubMed/NCBI | |
Gao F, Li M, Xiang R, Zhou X, Zhu L and Zhai Y: Expression of CLDN6 in tissues of gastric cancer patients: Association with clinical pathology and prognosis. Oncol Lett. 17:4621–4625. 2019.PubMed/NCBI | |
Rendón-Huerta E, Teresa F, Teresa GM, Xochitl GS, Georgina AF, Veronica ZZ and Montaño LF: Distribution and expression pattern of claudins 6, 7, and 9 in diffuse- and intestinal-type gastric adenocarcinomas. J Gastrointest Cancer. 41:52–59. 2010. View Article : Google Scholar : PubMed/NCBI | |
Lu YZ, Li Y, Zhang T and Han ST: Claudin-6 is down-regulated in gastric cancer and its potential pathway. Cancer Biomark. 28:329–340. 2020. View Article : Google Scholar : PubMed/NCBI | |
Resnick MB, Gavilanez M, Newton E, Konkin T, Bhattacharya B, Britt DE, Sabo E and Moss SF: Claudin expression in gastric adenocarcinomas: A tissue microarray study with prognostic correlation. Hum Pathol. 36:886–892. 2005. View Article : Google Scholar : PubMed/NCBI | |
Yu S, Zhang Y, Li Q, Zhang Z, Zhao G and Xu J: CLDN6 promotes tumor progression through the YAP1-snail1 axis in gastric cancer. Cell Death Dis. 10:9492019. View Article : Google Scholar : PubMed/NCBI | |
Torres-Martínez AC, Gallardo-Vera JF, Lara-Holguin AN, Montaño LF and Rendón-Huerta EP: Claudin-6 enhances cell invasiveness through claudin-1 in AGS human adenocarcinoma gastric cancer cells. Exp Cell Res. 350:226–235. 2017. View Article : Google Scholar : PubMed/NCBI | |
Chavarría-Velázquez CO, Torres-Martínez AC, Montaño LF and Rendón-Huerta EP: TLR2 activation induced by H. pylori LPS promotes the differential expression of claudin-4, −6, −7 and −9 via either STAT3 and ERK1/2 in AGS cells. Immunobiology. 223:38–48. 2018. View Article : Google Scholar : PubMed/NCBI | |
Zhu ZX, Huang JW, Liao MH and Zeng Y: Treatment strategy for hepatocellular carcinoma in China: Radiofrequency ablation versus liver resection. Jpn J Clin Oncol. 46:1075–1080. 2016.PubMed/NCBI | |
Zheng A, Yuan F, Li Y, Zhu F, Hou P, Li J, Song X, Ding M and Deng H: Claudin-6 and claudin-9 function as additional coreceptors for hepatitis C virus. J Virol. 81:12465–12471. 2007. View Article : Google Scholar : PubMed/NCBI | |
Osanai M, Takasawa A, Murata M and Sawada N: Claudins in cancer: Bench to bedside. Pflugers Arch. 469:55–67. 2017. View Article : Google Scholar : PubMed/NCBI | |
Huang L, Zhao C, Sun K, Yang D, Yan L, Luo D, He J, Hu X, Wang R, Shen X, et al: Downregulation of CLDN6 inhibits cell proliferation, migration, and invasion via regulating EGFR/AKT/mTOR signalling pathway in hepatocellular carcinoma. Cell Biochem Funct. 38:541–548. 2020. View Article : Google Scholar : PubMed/NCBI | |
Zhang X, Ruan Y, Li Y, Lin D and Quan C: Tight junction protein claudin-6 inhibits growth and induces the apoptosis of cervical carcinoma cells in vitro and in vivo. Med Oncol. 32:1482015. View Article : Google Scholar : PubMed/NCBI | |
Zhang X, Ruan Y, Li Y, Lin D, Liu Z and Quan C: Expression of apoptosis signal-regulating kinase 1 is associated with tight junction protein claudin-6 in cervical carcinoma. Int J Clin Exp Pathol. 8:5535–5541. 2015.PubMed/NCBI | |
Micke P, Mattsson JS, Edlund K, Lohr M, Jirström K, Berglund A, Botling J, Rahnenfuehrer J, Marincevic M, Pontén F, et al: Aberrantly activated claudin 6 and 18.2 as potential therapy targets in non-small-cell lung cancer. Int J Cancer. 135:2206–2214. 2014. View Article : Google Scholar : PubMed/NCBI | |
Wang Q, Zhang Y, Zhang T, Han ZG and Shan L: Low claudin-6 expression correlates with poor prognosis in patients with non-small cell lung cancer. Onco Targets Ther. 8:1971–1977. 2015.PubMed/NCBI | |
Wang L, Jin X, Lin D, Liu Z, Zhang X, Lu Y, Liu Y, Wang M, Yang M, Li J and Quan C: Clinicopathologic significance of claudin-6, occludin, and matrix metalloproteinases-2 expression in ovarian carcinoma. Diagn Pathol. 8:1902013. View Article : Google Scholar : PubMed/NCBI | |
Cao X and He GZ: Knockdown of CLDN6 inhibits cell proliferation and migration via PI3K/AKT/mTOR signaling pathway in endometrial carcinoma cell line HEC-1-B. Onco Targets Ther. 11:6351–6360. 2018. View Article : Google Scholar : PubMed/NCBI | |
Birks DK, Kleinschmidt-DeMasters BK, Donson AM, Barton VN, McNatt SA, Foreman NK and Handler MH: Claudin 6 is a positive marker for atypical teratoid/rhabdoid tumors. Brain Pathol. 20:140–150. 2010. View Article : Google Scholar : PubMed/NCBI | |
Sullivan LM, Yankovich T, Le P, Martinez D, Santi M, Biegel JA, Pawel BR and Judkins AR: Claudin-6 is a nonspecific marker for malignant rhabdoid and other pediatric tumors. Am J Surg Pathol. 36:73–80. 2012. View Article : Google Scholar : PubMed/NCBI | |
Antonelli M, Hasselblatt M, Haberler C, Di Giannatale A, Garrè ML, Donofrio V, Lauriola L, Ridola V, Arcella A, Frühwald M and Giangaspero F: Claudin-6 is of limited sensitivity and specificity for the diagnosis of atypical teratoid/rhabdoid tumors. Brain Pathol. 21:558–563. 2011.PubMed/NCBI | |
Tsunoda S, Smith E, De Young NJ, Wang X, Tian ZQ, Liu JF, Jamieson GG and Drew PA: Methylation of CLDN6, FBN2, RBP1, RBP4, TFPI2, and TMEFF2 in esophageal squamous cell carcinoma. Oncol Rep. 21:1067–1073. 2009. View Article : Google Scholar : PubMed/NCBI | |
Phi LTH, Sari IN, Yang YG, Lee SH, Jun N, Kim KS, Lee YK and Kwon HY: Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment. Stem Cells Int. 2018:54169232018. View Article : Google Scholar : PubMed/NCBI | |
Abdullah LN and Chow EK: Mechanisms of chemoresistance in cancer stem cells. Clin Transl Med. 2:32013. View Article : Google Scholar : PubMed/NCBI | |
Wang L, Xue Y, Shen Y, Li W, Cheng Y, Yan X, Shi W, Wang J, Gong Z, Yang G, et al: Claudin 6: A novel surface marker for characterizing mouse pluripotent stem cells. Cell Res. 22:1082–1085. 2012. View Article : Google Scholar : PubMed/NCBI | |
Turksen K and Troy TC: Claudin-6: A novel tight junction molecule is developmentally regulated in mouse embryonic epithelium. Dev Dyn. 222:292–300. 2001. View Article : Google Scholar : PubMed/NCBI | |
Gonzalez-Angulo AM, Morales-Vasquez F and Hortobagyi GN: Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 608:1–22. 2007. View Article : Google Scholar : PubMed/NCBI | |
Yang M, Li Y, Shen X, Ruan Y, Lu Y, Jin X, Song P, Guo Y, Zhang X, Qu H, et al: CLDN6 promotes chemoresistance through GSTP1 in human breast cancer. J Exp Clin Cancer Res. 36:1572017. View Article : Google Scholar : PubMed/NCBI | |
Yang M, Li Y, Ruan Y, Lu Y, Lin D, Xie Y, Dong B, Dang Q and Quan C: CLDN6 enhances chemoresistance to ADM via AF-6/ERKs pathway in TNBC cell line MDAMB231. Mol Cell Biochem. 443:169–180. 2018. View Article : Google Scholar : PubMed/NCBI | |
Chieffi P, De Martino M and Esposito F: New anti-cancer strategies in testicular germ cell tumors. Recent Pat Anticancer Drug Discov. 14:53–59. 2019. View Article : Google Scholar : PubMed/NCBI | |
Thomas A, Teicher BA and Hassan R: Antibody-drug conjugates for cancer therapy. Lancet Oncol. 17:e254–e262. 2016. View Article : Google Scholar : PubMed/NCBI | |
Birrer MJ, Moore KN, Betella I and Bates RC: Antibody-drug conjugate-based therapeutics: State of the science. J Natl Cancer Inst. 111:538–549. 2019. View Article : Google Scholar : PubMed/NCBI | |
Tsuchikama K and An Z: Antibody-drug conjugates: Recent advances in conjugation and linker chemistries. Protein Cell. 9:33–46. 2018. View Article : Google Scholar : PubMed/NCBI | |
Gudkov SV, Shilyagina NY, Vodeneev VA and Zvyagin AV: Targeted radionuclide therapy of human tumors. Int J Mol Sci. 17:332015. View Article : Google Scholar : PubMed/NCBI | |
Gill MR, Falzone N, Du Y and Vallis KA: Targeted radionuclide therapy in combined-modality regimens. Lancet Oncol. 18:e414–e423. 2017. View Article : Google Scholar : PubMed/NCBI | |
Schneider IC, Hartmann J, Braun G, Stitz J, Klamp T, Bihi M, Sahin U and Buchholz CJ: Displaying tetra-membrane spanning claudins on enveloped virus-like particles for cancer immunotherapy. Biotechnol J. 13:e17003452018. View Article : Google Scholar : PubMed/NCBI | |
Hutzler S, Erbar S, Jabulowsky RA, Hanauer JRH, Schnotz JH, Beissert T, Bodmer BS, Eberle R, Boller K, Klamp T, et al: Antigen-specific oncolytic MV-based tumor vaccines through presentation of selected tumor-associated antigens on infected cells or virus-like particles. Sci Rep. 7:168922017. View Article : Google Scholar : PubMed/NCBI | |
Kolokytha P, Yiannou P, Keramopoulos D, Kolokythas A, Nonni A, Patsouris E and Pavlakis K: Claudin-3 and claudin-4: Distinct prognostic significance in triple-negative and luminal breast cancer. Appl Immunohistochem Mol Morphol. 22:125–131. 2014. View Article : Google Scholar : PubMed/NCBI | |
Wu Z, Shi J, Song Y, Zhao J, Sun J, Chen X, Gao P and Wang Z: Claudin-7 (CLDN7) is overexpressed in gastric cancer and promotes gastric cancer cell proliferation, invasion and maintains mesenchymal state. Neoplasma. 65:349–359. 2018. View Article : Google Scholar : PubMed/NCBI | |
Danilova NV, Anikina KA, Oleynikova NA, Vychuzhanin DV and Malkov PG: Claudin-3 expression in gastric cancer. Arkh Patol. 82:5–11. 2020.(In Russian). View Article : Google Scholar : PubMed/NCBI | |
Liu JX, Wei ZY, Chen JS, Lu HC, Hao L and Li WJ: Prognostic and clinical significance of claudin-4 in gastric cancer: A meta-analysis. World J Surg Oncol. 13:2072015. View Article : Google Scholar : PubMed/NCBI |