Gene Symbol: claudin-1
Description: claudin 1
Alias: CLD1, ILVASC, SEMP1, claudin-1, senescence-associated epithelial membrane protein 1
Species: human
Products:     claudin-1

Top Publications

  1. Swisshelm K, Macek R, Kubbies M. Role of claudins in tumorigenesis. Adv Drug Deliv Rev. 2005;57:919-28 pubmed
    ..Future goals include understanding the biochemical and physiological mechanisms that are perturbed as a consequence of CLDN alterations in the progression of solid tumors. ..
  2. Andras I, Pu H, Deli M, Nath A, Hennig B, Toborek M. HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells. J Neurosci Res. 2003;74:255-65 pubmed
    ..Because tight junction proteins are critical for the barrier function of the BBB, such alterations can lead to disturbances of the BBB integrity and contribute to HIV trafficking into the brain. ..
  3. Ouban A, Ahmed A. Claudins in human cancer: a review. Histol Histopathol. 2010;25:83-90 pubmed publisher
    ..Thus, it seems that attempts to identify expression claudins in cancers are becoming increasingly useful in histologic diagnosis of tumors as well as means to assess patient's prognosis. ..
  4. Huo Q, Kinugasa T, Wang L, Huang J, Zhao J, Shibaguchi H, et al. Claudin-1 protein is a major factor involved in the tumorigenesis of colorectal cancer. Anticancer Res. 2009;29:851-7 pubmed
    ..CL-1 plays a pivotal role in cell morphology and behavior in the colonic epithelium. CL-1 protein may therefore be one of the major factors involved in the tumorigenesis of CRC. ..
  5. Moldvay J, Jackel M, Páska C, Soltesz I, Schaff Z, Kiss A. Distinct claudin expression profile in histologic subtypes of lung cancer. Lung Cancer. 2007;57:159-67 pubmed
  6. Kinugasa T, Akagi Y, Ochi T, Tanaka N, Kawahara A, Ishibashi Y, et al. Increased claudin-1 protein expression in hepatic metastatic lesions of colorectal cancer. Anticancer Res. 2012;32:2309-14 pubmed
    ..These observations suggest that CL-1 plays a pivotal role in the regulation of cellular morphology and in the behavior of metastatic processes in CRC. ..
  7. Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, et al. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol. 2002;156:1099-111 pubmed
    ..These findings provide the first evidence that continuous claudin-based TJs occur in the epidermis and that these TJs are crucial for the barrier function of the mammalian skin. ..
  8. Myal Y, Leygue E, Blanchard A. Claudin 1 in breast tumorigenesis: revelation of a possible novel "claudin high" subset of breast cancers. J Biomed Biotechnol. 2010;2010:956897 pubmed publisher
    ..In this paper, we discuss recent advances in our understanding of the potential role of claudin 1 in breast cancer...
  9. Paschoud S, Bongiovanni M, Pache J, Citi S. Claudin-1 and claudin-5 expression patterns differentiate lung squamous cell carcinomas from adenocarcinomas. Mod Pathol. 2007;20:947-54 pubmed
    ..These results indicate that characterization of tight junction protein expression in human lung tumors can be an additional diagnostic tool and provide new insights on their histogenesis. ..

More Information


  1. Meertens L, Bertaux C, Cukierman L, Cormier E, Lavillette D, Cosset F, et al. The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus. J Virol. 2008;82:3555-60 pubmed publisher
    ..Our work has generated novel and essential means to investigate the mechanism of HCV penetration into hepatocytes and the role of the claudin protein family in HCV dissemination, replication, and pathogenesis. ..
  2. Fortier A, Asselin E, Cadrin M. Keratin 8 and 18 loss in epithelial cancer cells increases collective cell migration and cisplatin sensitivity through claudin1 up-regulation. J Biol Chem. 2013;288:11555-71 pubmed publisher
    ..This is the first indication that modulation of K8/18 expression can influence the phenotype of epithelial cancer cells at a transcriptional level and supports the hypothesis that keratins play an active role in cancer progression. ..
  3. Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol. 1999;147:1351-63 pubmed
    ..In good agreement, PDZ1 and PDZ2 domains of ZO-1/ZO-2/ZO-3 were also recruited to claudin-based TJs, when introduced into cultured epithelial cells. The possible molecular architecture of TJ plaque structures is discussed. ..
  4. Shibutani M, Noda E, Maeda K, Nagahara H, Ohtani H, Hirakawa K. Low expression of claudin-1 and presence of poorly-differentiated tumor clusters correlate with poor prognosis in colorectal cancer. Anticancer Res. 2013;33:3301-6 pubmed
    ..The aim of this study was to determine the clinical significance of claudin-1 in terms of the cell-cell adhesion, considering the poorly-differentiated tumor component...
  5. Eftang L, Esbensen Y, Tannæs T, Blom G, Bukholm I, Bukholm G. Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival. BMC Cancer. 2013;13:586 pubmed publisher
  6. Morita K, Furuse M, Fujimoto K, Tsukita S. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci U S A. 1999;96:511-6 pubmed
    ..These findings indicated that multiple claudin family members are involved in the formation of TJ strands in various tissues. ..
  7. Lee J, Hsiao W, Chen H, Hsu L, Chen P, Lin M, et al. Upregulated claudin-1 expression confers resistance to cell death of nasopharyngeal carcinoma cells. Int J Cancer. 2010;126:1353-66 pubmed publisher
    ..In conclusion, our data demonstrate the regulation and novel biological function of claudin-1 and indicate the important role of claudin-1 in NPC tumorigenesis. ..
  8. Morohashi S, Kusumi T, Sato F, Odagiri H, Chiba H, Yoshihara S, et al. Decreased expression of claudin-1 correlates with recurrence status in breast cancer. Int J Mol Med. 2007;20:139-43 pubmed
    ..There was no significance between histological factors and CLDN4 expression. The results indicated that CLDN1 expression correlated with the recurrence status and malignant potential of breast cancer. ..
  9. Dhawan P, Singh A, Deane N, No Y, Shiou S, Schmidt C, et al. Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. J Clin Invest. 2005;115:1765-76 pubmed
    ..We further provide data suggesting that the regulation of E-cadherin expression and beta-catenin/Tcf signaling is a possible mechanism underlying claudin-1-dependent changes. ..
  10. Kondo J, Sato F, Kusumi T, Liu Y, Motonari O, Sato T, et al. Claudin-1 expression is induced by tumor necrosis factor-alpha in human pancreatic cancer cells. Int J Mol Med. 2008;22:645-9 pubmed
    ..These results suggest that claudin-1 expression is responsible for TNF-alpha-dependent growth signals and the proliferation of pancreatic cancer cells. ..
  11. Tokes A, Kulka J, Paku S, Szik A, Páska C, Novák P, et al. Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Breast Cancer Res. 2005;7:R296-305 pubmed
    ..The loss of CLDN4 expression in areas of apocrine metaplasia and in the majority of grade 1 invasive carcinomas also suggests a particular role for this protein in mammary glandular cell differentiation and carcinogenesis. ..
  12. Katoh M, Katoh M. CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family. Int J Mol Med. 2003;11:683-9 pubmed
    ..3, CLDN8 and CLDN17 on 21q22.11, CLDN21 and CLDN22 on 4q35.1. This is the first report on comprehensive characterization of CLDN23 gene, a candidate tumor suppressor gene implicated in intestinal-type gastric cancer. ..
  13. Tsukita S, Furuse M. Claudin-based barrier in simple and stratified cellular sheets. Curr Opin Cell Biol. 2002;14:531-6 pubmed
    ..Recent advances reveal that claudins - major cell adhesion molecules in tight junctions - are directly involved in this intercellular sealing, not only in simple but also in stratified cellular sheets in vertebrates. ..
  14. Ersoz S, Mungan S, Cobanoglu U, Turgutalp H, Ozoran Y. Prognostic importance of Claudin-1 and Claudin-4 expression in colon carcinomas. Pathol Res Pract. 2011;207:285-9 pubmed publisher
    ..Expression of Claudin-1 decreases significantly in the presence of lymph node metastasis and diminishes in mucinous carcinoma cases, indicating a negative correlation between Claudin-1 expression and neoplastic progression. ..
  15. Kramer F, White K, Kubbies M, Swisshelm K, Weber B. Genomic organization of claudin-1 and its assessment in hereditary and sporadic breast cancer. Hum Genet. 2000;107:249-56 pubmed
    ..Other regulatory or epigenetic factors may be involved in the down-regulation of this gene during breast cancer development. ..
  16. King J, Eugenin E, Buckner C, Berman J. HIV tat and neurotoxicity. Microbes Infect. 2006;8:1347-57 pubmed
    ..This review discusses the most recent data addressing tat-induced neurotoxicity and integrates these new findings in the context of NeuroAIDS. ..
  17. Raleigh D, Marchiando A, Zhang Y, Shen L, Sasaki H, Wang Y, et al. Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions. Mol Biol Cell. 2010;21:1200-13 pubmed publisher
    ..The data further suggest that these proteins are best considered as a group with both redundant and unique contributions to epithelial function and tight junction regulation. ..
  18. Coyne C, Gambling T, Boucher R, Carson J, Johnson L. Role of claudin interactions in airway tight junctional permeability. Am J Physiol Lung Cell Mol Physiol. 2003;285:L1166-78 pubmed
    ..These suggest that airway TJs are regulated by claudinclaudin interactions that confer the selectivity of the junction. ..
  19. Gonzalez Mariscal L, Betanzos A, Nava P, Jaramillo B. Tight junction proteins. Prog Biophys Mol Biol. 2003;81:1-44 pubmed
  20. Nemeth J, Nemeth Z, Tátrai P, Péter I, Somorácz A, Szasz A, et al. High expression of claudin-1 protein in papillary thyroid tumor and its regional lymph node metastasis. Pathol Oncol Res. 2010;16:19-27 pubmed publisher
    ..Based on these results, claudin-1 may be a useful tumor marker for PTC. ..
  21. Liu S, Yang W, Shen L, Turner J, Coyne C, Wang T. Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection. J Virol. 2009;83:2011-4 pubmed publisher
    ..The altered TJ protein expression may contribute to the morphological and functional changes observed in HCV-infected hepatocytes. ..
  22. Akasaka H, Sato F, Morohashi S, Wu Y, Liu Y, Kondo J, et al. Anti-apoptotic effect of claudin-1 in tamoxifen-treated human breast cancer MCF-7 cells. BMC Cancer. 2010;10:548 pubmed publisher
    ..These results indicate that claudin-1 has anti-apoptotic effects, and is involved in the regulation of the expression and subcellular localization of ?-catenin and E-cadherin in MCF-7, but not T47 D cells. ..
  23. Raleigh D, Boe D, Yu D, Weber C, Marchiando A, Bradford E, et al. Occludin S408 phosphorylation regulates tight junction protein interactions and barrier function. J Cell Biol. 2011;193:565-82 pubmed publisher
  24. Miyamoto K, Kusumi T, Sato F, Kawasaki H, Shibata S, Ohashi M, et al. Decreased expression of claudin-1 is correlated with recurrence status in esophageal squamous cell carcinoma. Biomed Res. 2008;29:71-6 pubmed
    ..0045). The results indicated that claudin-1 expression was correlated with the recurrence status and poor prognosis in esophageal cancer and claudin-1 expression may be a good indicator of recurrence in esophageal cancer. ..
  25. Miwa N, Furuse M, Tsukita S, Niikawa N, Nakamura Y, Furukawa Y. Involvement of claudin-1 in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers. Oncol Res. 2001;12:469-76 pubmed
    ..Our results imply that claudin-1 is involved in the beta-catenin-Tcf/LEF signaling pathway, and that increased expression of claudin-1 may have some role in colorectal tumorigenesis. ..
  26. Weber C, Nalle S, Tretiakova M, Rubin D, Turner J. Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation. Lab Invest. 2008;88:1110-20 pubmed publisher
    ..We speculate that increased claudin-1 and claudin-2 expression may be involved at early stages of transformation in IBD-associated neoplasia. ..
  27. Kovalenko O, Yang X, Hemler M. A novel cysteine cross-linking method reveals a direct association between claudin-1 and tetraspanin CD9. Mol Cell Proteomics. 2007;6:1855-67 pubmed
  28. Swisshelm K, Machl A, Planitzer S, Robertson R, Kubbies M, Hosier S. SEMP1, a senescence-associated cDNA isolated from human mammary epithelial cells, is a member of an epithelial membrane protein superfamily. Gene. 1999;226:285-95 pubmed
    We have cloned a human cDNA, SEMP1 (senescence-associated epithelial membrane protein 1), using differential display (DD) of mRNA...
  29. Miyamori H, Takino T, Kobayashi Y, Tokai H, Itoh Y, Seiki M, et al. Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases. J Biol Chem. 2001;276:28204-11 pubmed
    ..These results suggest that claudin recruits all MT-MMPs and pro-MMP-2 on the cell surface to achieve elevated focal concentrations and, consequently, enhances activation of pro-MMP-2. ..
  30. Harris H, Davis C, Mullins J, Hu K, Goodall M, Farquhar M, et al. Claudin association with CD81 defines hepatitis C virus entry. J Biol Chem. 2010;285:21092-102 pubmed publisher
  31. Singh A, Sharma A, Dhawan P. Claudin-1 expression confers resistance to anoikis in colon cancer cells in a Src-dependent manner. Carcinogenesis. 2012;33:2538-47 pubmed publisher
    ..Our findings are of direct clinical relevance and may open new therapeutic opportunity in colon cancer treatment and/or management. ..
  32. Krishnan M, Singh A, Smith J, Sharma A, Chen X, Eschrich S, et al. HDAC inhibitors regulate claudin-1 expression in colon cancer cells through modulation of mRNA stability. Oncogene. 2010;29:305-12 pubmed publisher
    ..As HDAC inhibitors are considered to be promising anticancer drugs, these new findings will have implications in both laboratory and clinical settings. ..
  33. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2:285-93 pubmed
    ..New insights into the molecular architecture of tight junctions allow us to now discuss the structure and functions of this unique cell-cell adhesion apparatus in molecular terms. ..
  34. Chang T, Ito K, Ko T, Liu Q, Salto Tellez M, Yeoh K, et al. Claudin-1 has tumor suppressive activity and is a direct target of RUNX3 in gastric epithelial cells. Gastroenterology. 2010;138:255-65.e1-3 pubmed publisher
    ..Claudin-1 is down-regulated during the epithelial-mesenchymal transition; RUNX3 might therefore act as a tumor suppressor to antagonize the epithelial-mesenchymal transition. ..
  35. Yang W, Qiu C, Biswas N, Jin J, Watkins S, Montelaro R, et al. Correlation of the tight junction-like distribution of Claudin-1 to the cellular tropism of hepatitis C virus. J Biol Chem. 2008;283:8643-53 pubmed publisher
    ..5.1 cells to HCV infection. Our results suggest that the specific localization pattern of CLDN1 may be crucial in the regulation of HCV cellular tropism. ..
  36. Harris H, Farquhar M, Mee C, Davis C, Reynolds G, Jennings A, et al. CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry. J Virol. 2008;82:5007-20 pubmed publisher
  37. Grone J, Weber B, Staub E, Heinze M, Klaman I, Pilarsky C, et al. Differential expression of genes encoding tight junction proteins in colorectal cancer: frequent dysregulation of claudin-1, -8 and -12. Int J Colorectal Dis. 2007;22:651-9 pubmed
    ..CLDN1 is frequently up-regulated in large proportion of CRC and may represent potential target molecule for blocking studies in CRC. ..
  38. Martínez Estrada O, Cullerés A, Soriano F, Peinado H, Bolós V, Martinez F, et al. The transcription factors Slug and Snail act as repressors of Claudin-1 expression in epithelial cells. Biochem J. 2006;394:449-57 pubmed
    ..Taken together, these results support the hypothesis that Claudin-1 is a direct downstream target gene of Snail family factors in epithelial cells. ..
  39. Furuse M, Sasaki H, Tsukita S. Manner of interaction of heterogeneous claudin species within and between tight junction strands. J Cell Biol. 1999;147:891-903 pubmed
    ..We concluded that distinct species of claudins can interact within and between TJ strands, except in some combinations. This mode of assembly of claudins could increase the diversity of the structure and functions of TJ strands. ..
  40. Suh Y, Yoon C, Kim R, Lim E, Oh Y, Hwang S, et al. Claudin-1 induces epithelial-mesenchymal transition through activation of the c-Abl-ERK signaling pathway in human liver cells. Oncogene. 2013;32:4873-82 pubmed publisher
    ..The present observations suggest that CLDN1 could be exploited as a biomarker for liver cancer metastasis and might provide a pivotal point for therapeutic intervention in HCC. ..
  41. Abdelzaher E, Rizk A, Bessa S, Omer K. Predictive value of immunohistochemical expression of claudin-1 in colonic carcinoma. J Egypt Natl Canc Inst. 2011;23:123-31 pubmed publisher
    ..Claudin-1 expression could be used as a predictor of colonic carcinoma stage and lymph node status with a high sensitivity and specificity. ..
  42. Huang J, Li J, Qu Y, Zhang J, Zhang L, Chen X, et al. The expression of claudin 1 correlates with ?-catenin and is a prognostic factor of poor outcome in gastric cancer. Int J Oncol. 2014;44:1293-301 pubmed publisher
    b>Claudin 1 is one of the tight junction proteins, which are critical in the maintenance of epithelial integrity. Aberrant regulation of CLDN1 and its correlation with ?-catenin have been discovered in malignant tumors...
  43. Nakagawa S, Miyoshi N, Ishii H, Mimori K, Tanaka F, Sekimoto M, et al. Expression of CLDN1 in colorectal cancer: a novel marker for prognosis. Int J Oncol. 2011;39:791-6 pubmed publisher
    ..In conclusion, the present data strongly suggest that CLDN1 expression is a prognostic factor in CRC patients. ..
  44. Hamazaki Y, Itoh M, Sasaki H, Furuse M, Tsukita S. Multi-PDZ domain protein 1 (MUPP1) is concentrated at tight junctions through its possible interaction with claudin-1 and junctional adhesion molecule. J Biol Chem. 2002;277:455-61 pubmed
  45. Fofana I, Krieger S, Grunert F, Glauben S, Xiao F, Fafi Kremer S, et al. Monoclonal anti-claudin 1 antibodies prevent hepatitis C virus infection of primary human hepatocytes. Gastroenterology. 2010;139:953-64, 964.e1-4 pubmed publisher
    ..Monoclonal antibodies against the HCV entry factor CLDN1 might be used to prevent HCV infection, such as after liver transplantation, and might also restrain virus spread in chronically infected patients. ..
  46. Evans M, von Hahn T, Tscherne D, Syder A, Panis M, Wölk B, et al. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature. 2007;446:801-5 pubmed
    ..With CLDN1 we have identified a novel key factor for HCV entry and a new target for antiviral drug development. ..
  47. Wu Y, Zhang S, Wang G, Chen Y. Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion. World J Gastroenterol. 2008;14:4943-8 pubmed
    ..Further study is needed to elucidate the precise mechanism and the relation of claudin-1 expression with the neoplasm progress. ..
  48. Yoshida T, Kinugasa T, Akagi Y, Kawahara A, Romeo K, Shiratsuchi I, et al. Decreased expression of claudin-1 in rectal cancer: a factor for recurrence and poor prognosis. Anticancer Res. 2011;31:2517-25 pubmed
    ..Loss of claudin-1 expression is a strong predictor of disease recurrence and poor patient survival in stage II and III rectal cancer. ..
  49. Hadj Rabia S, Baala L, Vabres P, Hamel Teillac D, Jacquemin E, Fabre M, et al. Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology. 2004;127:1386-90 pubmed
    ..Bile duct injury may be related to the absence of claudin-1 expression in cholangiocytes. Our observation, in conjunction with ZO-2-associated hypercholanemia, emphasizes the role played by TJ components in hereditary cholestasis. ..
  50. Yoon C, Kim M, Park M, Park I, Hwang S, An S, et al. Claudin-1 acts through c-Abl-protein kinase Cdelta (PKCdelta) signaling and has a causal role in the acquisition of invasive capacity in human liver cells. J Biol Chem. 2010;285:226-33 pubmed publisher
    ..The present observations raise the possibility of exploiting claudin-1 as a potential biomarker for the spread of liver cancer and might provide pivotal points for therapeutic intervention in HCC. ..
  51. Cukierman L, Meertens L, Bertaux C, Kajumo F, Dragic T. Residues in a highly conserved claudin-1 motif are required for hepatitis C virus entry and mediate the formation of cell-cell contacts. J Virol. 2009;83:5477-84 pubmed publisher
    ..However, these mutants no longer localized to cell-cell contacts. Based on our observations, we propose that cell-cell contacts formed by claudin-1 may generate specialized membrane domains that are amenable to HCV entry. ..
  52. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998;141:1539-50 pubmed
  53. Koizumi H, Suzuki H, Ohbuchi T, Kitamura T, Hashida K, Nakamura M. Increased permeability of the epithelium of middle ear cholesteatoma. Clin Otolaryngol. 2015;40:106-14 pubmed publisher
    ..This evidence supports the acid lysis hypothesis of bone resorption in cholesteatoma. ..
  54. Neuhaus W, Wirth M, Plattner V, Germann B, Gabor F, Noe C. Expression of Claudin-1, Claudin-3 and Claudin-5 in human blood-brain barrier mimicking cell line ECV304 is inducible by glioma-conditioned media. Neurosci Lett. 2008;446:59-64 pubmed publisher
    ..For the first time this study proves the presence of Claudin-1, Claudin-3 and Claudin-5 in ECV304 (obtained from ECACC) cell layers and the inducibility of their expression by glioma-conditioned media. ..