The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CLDN1  -  claudin 1

Homo sapiens

Synonyms: CLD1, Claudin-1, ILVASC, SEMP1, Senescence-associated epithelial membrane protein, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CLDN1

  • In the sporadic tumors and hereditary breast cancer patients, we have found no evidence to support the involvement of aberrant CLDN1 in breast tumorigenesis [1].
  • CLDN1 may support tumor suppressive functions in tissues such as the brain, where dramatic loss of expression has been demonstrated in glioblastoma multiforme [2].
  • We documented increased expression of CLDN1 in all 16 primary colorectal cancers we examined, compared with adjacent noncancerous mucosae [3].
  • CONCLUSIONS: The significant loss of CLDN1 protein in breast cancer cells suggests that CLDN1 may play a role in invasion and metastasis [4].
  • CLDN1 was present in the membrane of normal duct cells and in some of the cell membranes from ductal carcinoma in situ, and was frequently observed in eight out of nine areas of apocrine metaplasia, whereas invasive tumours were negative for CLDN1 or it was present in a scattered distribution among such tumour cells (in 36/39 malignant tumours) [4].

High impact information on CLDN1

  • The claudin family of genes is known to express protein components of tight junctions in other tissues [5].
  • Genetic manipulations of claudin-1 expression in colon cancer cell lines induced changes in cellular phenotype, with structural and functional changes in markers of epithelial-mesenchymal transition [6].
  • Here, we report an increased expression of claudin-1 in human primary colon carcinoma and metastasis and in cell lines derived from primary and metastatic tumors [6].
  • Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer [6].
  • To test whether members of the claudin family of tight junction proteins influence paracellular ionic selectivity, we expressed human claudin-4 in cultured MDCK cells using an inducible promoter [7].

Biological context of CLDN1


Anatomical context of CLDN1

  • Recently, a claudin-1 (CLDN1) cDNA has been isolated from human mammary epithelial cells (HMECs) [1].
  • Likewise, in the breast cancer cell lines, no genetic alterations in the promoter or coding sequences have been identified that would explain the loss of CLDN1 expression [1].
  • Two related integral membrane proteins, claudin-1 and -2, recently were identified as novel components of tight junction (TJ) strands [8].
  • Moderate claudin 1 and ZO-1 membranous staining were present, whereas only focal weak claudin 3 and 4 membranous staining was present in normal gastric epithelium [11].
  • Consistent with this difference in barrier function, claudins expressed by HFL cells cultured in DCI medium were tightly localized to the plasma membrane; however, claudins expressed by HFL cells cultured in control medium accumulated in an intracellular compartment and showed discontinuities in claudin plasma membrane localization [12].

Associations of CLDN1 with chemical compounds


Co-localisations of CLDN1

  • MT1-MMP was co-localized with claudin-1 not only at cell-cell borders, but also at other parts of the cells [10].

Regulatory relationships of CLDN1


Other interactions of CLDN1

  • 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 [10].
  • Furthermore, dendritic cells (DCs) of the medulla, with a major role for selection of thymocytes, expressed CLDN-1 and OCLN as well, implying that the interposition of DCs within the mTEC scaffold is also helped by TJs [18].
  • Quantification performed determining the expression for TJ-molecules displayed diminished expression for CLDN-1 (p<0.01) and CLDN-5 (p<0.01) in patients with chronic venous insufficiency in comparison with healthy controls on mRNA as well as protein level [19].
  • Our results indicate that occludin, claudin 1 and claudin 3 are involved in cell-to-cell contacts between keratinocytes in human epidermis, although their functional importance remains unknown [20].
  • CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family [21].

Analytical, diagnostic and therapeutic context of CLDN1

  • METHODS: Altogether, 56 sections from 52 surgically resected breast specimens were analyzed for CLDN1, CLDN3 and CLDN4 expression by immunohistochemistry. mRNA was also analyzed using real-time PCR in 17 of the 52 cases [4].
  • Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues [22].
  • We characterized the claudin expression in normal airways removed from human donors during lung transplantation and determined the contribution of each claudin to airway barrier function [23].
  • The cellular immunofluorescence analysis of CLDN1 protein expression in transduced bulk cultures revealed a CLDN1-positive subfraction with a heterogeneous pattern of membrane and cytosolic immunostaining [24].
  • In this report, we investigated the physiologic role of CLDN1 in CLDN1-transduced MDA-MB 361 breast tumor cells in adherent 2D and suspension 3D spheroid cell cultures [24].


  1. Genomic organization of claudin-1 and its assessment in hereditary and sporadic breast cancer. Krämer, F., White, K., Kubbies, M., Swisshelm, K., Weber, B.H. Hum. Genet. (2000) [Pubmed]
  2. Role of claudins in tumorigenesis. Swisshelm, K., Macek, R., Kubbies, M. Adv. Drug Deliv. Rev. (2005) [Pubmed]
  3. Involvement of claudin-1 in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers. Miwa, N., Furuse, M., Tsukita, S., Niikawa, N., Nakamura, Y., Furukawa, Y. Oncol. Res. (2000) [Pubmed]
  4. Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Tokés, A.M., Kulka, J., Paku, S., Szik, A., Páska, C., Novák, P.K., Szilák, L., Kiss, A., Bögi, K., Schaff, Z. Breast Cancer Res. (2005) [Pubmed]
  5. Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29. Wilcox, E.R., Burton, Q.L., Naz, S., Riazuddin, S., Smith, T.N., Ploplis, B., Belyantseva, I., Ben-Yosef, T., Liburd, N.A., Morell, R.J., Kachar, B., Wu, D.K., Griffith, A.J., Riazuddin, S., Friedman, T.B. Cell (2001) [Pubmed]
  6. Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. Dhawan, P., Singh, A.B., Deane, N.G., No, Y., Shiou, S.R., Schmidt, C., Neff, J., Washington, M.K., Beauchamp, R.D. J. Clin. Invest. (2005) [Pubmed]
  7. Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability. Van Itallie, C., Rahner, C., Anderson, J.M. J. Clin. Invest. (2001) [Pubmed]
  8. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Morita, K., Furuse, M., Fujimoto, K., Tsukita, S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Agarwal, R., D'Souza, T., Morin, P.J. Cancer Res. (2005) [Pubmed]
  10. Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases. Miyamori, H., Takino, T., Kobayashi, Y., Tokai, H., Itoh, Y., Seiki, M., Sato, H. J. Biol. Chem. (2001) [Pubmed]
  11. Claudin expression in gastric adenocarcinomas: a tissue microarray study with prognostic correlation. Resnick, M.B., Gavilanez, M., Newton, E., Konkin, T., Bhattacharya, B., Britt, D.E., Sabo, E., Moss, S.F. Hum. Pathol. (2005) [Pubmed]
  12. Developmental regulation of claudin localization by fetal alveolar epithelial cells. Daugherty, B.L., Mateescu, M., Patel, A.S., Wade, K., Kimura, S., Gonzales, L.W., Guttentag, S., Ballard, P.L., Koval, M. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  13. Novel effects of azithromycin on tight junction proteins in human airway epithelia. Asgrimsson, V., Gudjonsson, T., Gudmundsson, G.H., Baldursson, O. Antimicrob. Agents Chemother. (2006) [Pubmed]
  14. The roles of claudin superfamily proteins in paracellular transport. Heiskala, M., Peterson, P.A., Yang, Y. Traffic (2001) [Pubmed]
  15. theta Isoform of protein kinase C alters barrier function in intestinal epithelium through modulation of distinct claudin isotypes: a novel mechanism for regulation of permeability. Banan, A., Zhang, L.J., Shaikh, M., Fields, J.Z., Choudhary, S., Forsyth, C.B., Farhadi, A., Keshavarzian, A. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  16. Claudins regulate the intestinal barrier in response to immune mediators. Kinugasa, T., Sakaguchi, T., Gu, X., Reinecker, H.C. Gastroenterology (2000) [Pubmed]
  17. Epidermal growth factor receptor activation differentially regulates claudin expression and enhances transepithelial resistance in Madin-Darby canine kidney cells. Singh, A.B., Harris, R.C. J. Biol. Chem. (2004) [Pubmed]
  18. Cellular Networks of Human Thymic Medullary Stromas Coordinated by p53-Related Transcription Factors. Ichimiya, S., Kojima, T. J. Histochem. Cytochem. (2006) [Pubmed]
  19. Tight junctions and compression therapy in chronic venous insufficiency. Herouy, Y., Kahle, B., Idzko, M., Eberth, I., Norgauer, J., Pannier, F., Rabe, E., Jünger, M., Bruckner-Tuderman, L. Int. J. Mol. Med. (2006) [Pubmed]
  20. Tight junction proteins: a novel class of integral membrane proteins. Expression in human epidermis and in HaCaT keratinocytes. Tebbe, B., Mankertz, J., Schwarz, C., Amasheh, S., Fromm, M., Assaf, C., Schultz-Ehrenburg, U., Sánchez Ruderish, H., Schulzke, J.D., Orfanos, C.E. Arch. Dermatol. Res. (2002) [Pubmed]
  21. CLDN23 gene, frequently down-regulated in intestinal-type gastric cancer, is a novel member of CLAUDIN gene family. Katoh, M., Katoh, M. Int. J. Mol. Med. (2003) [Pubmed]
  22. The claudin gene family: expression in normal and neoplastic tissues. Hewitt, K.J., Agarwal, R., Morin, P.J. BMC Cancer (2006) [Pubmed]
  23. Role of claudin interactions in airway tight junctional permeability. Coyne, C.B., Gambling, T.M., Boucher, R.C., Carson, J.L., Johnson, L.G. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  24. Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids. Hoevel, T., Macek, R., Swisshelm, K., Kubbies, M. Int. J. Cancer (2004) [Pubmed]
WikiGenes - Universities