TY - JOUR
T1 - Claudin-1, a double-edged sword in cancer
AU - Bhat, Ajaz A.
AU - Syed, Najeeb
AU - Therachiyil, Lubna
AU - Nisar, Sabah
AU - Hashem, Sheema
AU - Macha, Muzafar A.
AU - Yadav, Santosh K.
AU - Krishnankutty, Roopesh
AU - Muralitharan, Shanmugakonar
AU - Al-Naemi, Hamda
AU - Bagga, Puneet
AU - Reddy, Ravinder
AU - Dhawan, Punita
AU - Akobeng, Anthony
AU - Uddin, Shahab
AU - Frenneaux, Michael P.
AU - El-Rifai, Wael
AU - Haris, Mohammad
N1 - Funding Information:
Acknowledgements: The authors would like to express their gratitude to Vineeta Tanwar (Research Scientist, Ohio State University, Ohio, Columbus, USA) for help in English editing and valuable suggestions to improve the quality of the manuscript. The publication of this article was funded by the Qatar National Library.
Funding Information:
This research was funded by Sidra Medicine to Mohammad Haris (50610110002) and Ajaz A. Bhat (5011041002). Muzafar A. Macha is a recipient of Ramanujan Fellowship from Science and Engineering Research Board (SERB), Department of Science and Technology, Govt. of India, New Delhi. The authors would like to express their gratitude to Vineeta Tanwar (Research Scientist, Ohio State University, Ohio, Columbus, USA) for help in English editing and valuable suggestions to improve the quality of the manuscript. The publication of this article was funded by the Qatar National Library.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - Claudin 1
KW - Epithelial to mesenchymal transition
KW - Metastasis
KW - Tight junctions
KW - Tumor
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U2 - 10.3390/ijms21020569
DO - 10.3390/ijms21020569
M3 - Review article
C2 - 31952355
AN - SCOPUS:85077981080
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 2
M1 - 569
ER -