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Claudin-1, A Double-Edged Sword in Cancer

Division of Translational Medicine, Research Branch, Sidra Medicine, Doha 26999, Qatar
Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar
Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar
Department of Biotechnology, Central University of Kashmir, Ganderbal, Jammu and Kashmir 191201, India
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Laboratory Animal Research Center, Qatar University, Doha 2713, Qatar
Center for Magnetic Resonance and Optical Imaging, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
Department of Pediatric Gastroenterology, Sidra Medicine, Doha 26999, Qatar
Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar
Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 569;
Received: 25 November 2019 / Revised: 12 January 2020 / Accepted: 13 January 2020 / Published: 15 January 2020
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
Claudins, a group of membrane proteins involved in the formation of tight junctions, are mainly found in endothelial or epithelial cells. These proteins have attracted much attention in recent years and have been implicated and studied in a multitude of diseases. Claudins not only regulate paracellular transepithelial/transendothelial transport but are also critical for cell growth and differentiation. Not only tissue-specific but the differential expression in malignant tumors is also the focus of claudin-related research. In addition to up- or down-regulation, claudin proteins also undergo delocalization, which plays a vital role in tumor invasion and aggressiveness. Claudin (CLDN)-1 is the most-studied claudin in cancers and to date, its role as either a tumor promoter or suppressor (or both) is not established. In some cancers, lower expression of CLDN-1 is shown to be associated with cancer progression and invasion, while in others, loss of CLDN-1 improves the patient survival. Another topic of discussion regarding the significance of CLDN-1 is its localization (nuclear or cytoplasmic vs perijunctional) in diseased states. This article reviews the evidence regarding CLDN-1 in cancers either as a tumor promoter or suppressor from the literature and we also review the literature regarding the pattern of CLDN-1 distribution in different cancers, focusing on whether this localization is associated with tumor aggressiveness. Furthermore, we utilized expression data from The Cancer Genome Atlas (TCGA) to investigate the association between CLDN-1 expression and overall survival (OS) in different cancer types. We also used TCGA data to compare CLDN-1 expression in normal and tumor tissues. Additionally, a pathway interaction analysis was performed to investigate the interaction of CLDN-1 with other proteins and as a future therapeutic target. View Full-Text
Keywords: claudin 1; tight junctions; tumor; metastasis; epithelial to mesenchymal transition claudin 1; tight junctions; tumor; metastasis; epithelial to mesenchymal transition
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Bhat, A.A.; Syed, N.; Therachiyil, L.; Nisar, S.; Hashem, S.; Macha, M.A.; Yadav, S.K.; Krishnankutty, R.; Muralitharan, S.; Al-Naemi, H.; Bagga, P.; Reddy, R.; Dhawan, P.; Akobeng, A.; Uddin, S.; Frenneaux, M.P.; El-Rifai, W.; Haris, M. Claudin-1, A Double-Edged Sword in Cancer. Int. J. Mol. Sci. 2020, 21, 569.

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