Claudin-1, a double-edged sword in cancer

Ajaz A. Bhat, Najeeb Syed, Lubna Therachiyil, Sabah Nisar, Sheema Hashem, Muzafar A. Macha, Santosh K. Yadav, Roopesh Krishnankutty, Shanmugakonar Muralitharan, Hamda Al-Naemi, Puneet Bagga, Ravinder Reddy, Punita Dhawan, Anthony Akobeng, Shahab Uddin, Michael P. Frenneaux, Wael El-Rifai, Mohammad Haris

Research output: Contribution to journalReview article

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number569
JournalInternational journal of molecular sciences
Volume21
Issue number2
DOIs
StatePublished - Jan 2 2020

Keywords

  • Claudin 1
  • Epithelial to mesenchymal transition
  • Metastasis
  • Tight junctions
  • Tumor

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    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. (2020). Claudin-1, a double-edged sword in cancer. International journal of molecular sciences, 21(2), [569]. https://doi.org/10.3390/ijms21020569