The claudin family of proteins in human malignancy: a clinical perspective

Lei Ding; Zhe Lu; Qun Lu; Yan-Hua Chen
November 2013
Cancer Management & Research;2013, Vol. 5, p367
Academic Journal
Tight junctions, or zonula occludens, are the most apical component of the junctional complex and provide one form of cell-cell adhesion in epithelial and endothelial cells. Nearly 90% of malignant tumors are derived from the epithelium. Loss of cell-cell adhesion is one of the steps in the progression of cancer to metastasis. At least three main tight junction family proteins have been discovered: occludin, claudin, and junctional adhesion molecule (JAM). Claudins are the most important structural and functional components of tight junction integral membrane proteins, with at least 24 members in mammals. They are crucial for the paracellular flux of ions and small molecules. Overexpression or downregulation of claudins is frequently observed in epithelial-derived cancers. However, molecular mechanisms by which claudins affect tumorigenesis remain largely unknown. As the pivotal proteins in epithelial cells, altered expression and distribution of different claudins have been reported in a wide variety of human malignancies, including pancreatic, colonic, lung, ovarian, thyroid, prostate, esophageal, and breast cancers. In this review, we will give the readers an overall picture of the changes in claudin expression observed in various cancers and their mechanisms of regulation. Downregulation of claudins contributes to epithelial transformation by increasing the paracellular permeability of nutrients and growth factors to cancerous cells. In the cases of upregulation of claudin expression, the barrier function of the cancerous epithelia changes, as they often display a disorganized arrangement of tight junction strands with increased permeability to paracellular markers. Finally, we will summarize the literature suggesting that claudins may become useful biomarkers for cancer detection and diagnosis as well as possible therapeutic targets for cancer treatment.


Related Articles

  • Contribution of Tight Junction Proteins to Ion, Macromolecule, and Water Barrier in Keratinocytes. Kirschner, Nina; Rosenthal, Rita; Furuse, Mikio; Moll, Ingrid; Fromm, Michael; Brandner, Johanna M // Journal of Investigative Dermatology;May2013, Vol. 133 Issue 5, p1161 

    Tight junctions (TJs) form a selective barrier for ions, water, and macromolecules in simple epithelia. In keratinocytes and epidermis, TJs were shown to be involved in individual barrier functions. The absence of the TJ protein claudin-1 (Cldn1) in mice results in a skin-barrier defect...

  • Claudin-1 as a promoter of EMT in hepatocellular carcinoma. Stebbing, J; Filipović, A; Giamas, G // Oncogene;10/10/2013, Vol. 32 Issue 41, p4871 

    Claudins are integral structural and functional components of apical cell adhesions (tight junctions). Loss of such adhesions has been associated with malignant transformation, a process most often accompanied by a concomitant loss of claudin expression. A growing body of evidence reveals the...

  • Regulation of the Epithelial-Mesenchymal Transition by Claudin-3 and Claudin-4. Lin, Xinjian; Shang, Xiying; Manorek, Gerald; Howell, Stephen B. // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    The mechanisms that control intracellular adhesion are central to the process of invasion and metastasis. Claudin-3 (CLDN3) and claudin-4 (CLDN4) are major structural molecules of the tight junctions that link epithelial cells. Our prior work has demonstrated that knockdown of the expression of...

  • Claudins and renal salt transport. Muto, Shigeaki; Furuse, Mikio; Kusano, Eiji // Clinical & Experimental Nephrology;Feb2012, Vol. 16 Issue 1, p61 

    Tight junctions (TJs) are the most apical component of junctional complexes and regulate the movement of electrolytes and solutes by the paracellular pathway across epithelia. The defining ultrastructural features of TJs are strands of transmembrane protein particles that adhere to similar...

  • Molecular Architecture of Tight Junctions of Periderm Differs From That of the Maculae Occludentes of Epidermis. Morita, Kazumasa; Furuse, Mikio; Yoshida, Yoko; Itoh, Masahiko; Sasaki, Hiroyuki; Tsukita, Shoichiro; Miyachi, Yoshiki // Journal of Investigative Dermatology;Jun2002, Vol. 118 Issue 6, p1073 

    Occludin and claudins are tetraspan-transmembrane proteins in tight junctions. Maculae occludentes, which are less-developed tight junctions, occur in the granular cell layer of the epidermis. The periderm, which overlies the developing epidermis and functions as a protective layer for the...

  • Role of tight junction claudins in biological systems -- more than a simple paracellular barrier in inflammation and metabolism. Tsukita, S. // Proceedings of the Physiological Society;2013, p226P 

    The tight junction (TJ) system is primarily responsible for establishing the paracellular barrier function of epithelial cell sheets. The TJ is a supramolecular complex containing transmembrane proteins associated with membrane-scaffolding proteins such as ZO-1/2 and cingulin that allows the...

  • Identifying proteins and protein networks of the tight junction. Anderson, J.; Van Itallie, C. M. // Proceedings of the Physiological Society;2013, p226P 

    The proteins and functional protein networks of the tight junction remain incompletely defined. Among the currently known proteins are barrier forming proteins like occludin and the claudin family, scaffolding proteins like ZO-1 and some cytoskeletal, signaling and cell polarity proteins. To...

  • RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation. Jones, Robert A.; Robinson, Tyler J.; Liu, Jeff C.; Shrestha, Mariusz; Voisin, Veronique; YoungJun Ju; Chung, Philip E. D.; Pellecchia, Giovanna; Fell, Victoria L.; SooIn Bae; Muthuswamy, Lakshmi; Datti, Alessandro; Egan, Sean E.; Zhe Jiang; Leone, Gustavo; Bader, Gary D.; Schimmer, Aaron; Zacksenhaus, Eldad; Ju, YoungJun; Bae, SooIn // Journal of Clinical Investigation;Oct2016, Vol. 126 Issue 10, p3739 

    Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great...

  • Guanine nucleotide-binding protein Gαi2: a new partner of claudin-5 that regulates tight junction integrity in human brain endothelial cells. Luissint, Anny-Claude; Federici, Christian; Guillonneau, François; Chrétien, Fabrice; Camoin, Luc; Glacial, Fabienne; Ganeshamoorthy, Kayathiri; Couraud, Pierre-Olivier // Journal of Cerebral Blood Flow & Metabolism;May2012, Vol. 32 Issue 5, p860 

    The blood-brain barrier (BBB) selectively controls the exchanges between the blood and the brain: it is formed by tight junctions (TJs) between adjacent microvascular endothelial cells. The transmembrane protein claudin-5 is known as a key TJ protein at the BBB, although, the molecular...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics