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Tight Junctions and Signaling Pathways in Cancer

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Tight Junctions in Inflammation and Cancer

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Abstract

Tight junctions (TJs) are intercellular connections that close the gap between the individual cells and limit the paracellular entry of harmful antigens, toxins, microbes, etc. In addition, they also regulate vesicle trafficking, signal transduction, transcription, and cytoskeletal dynamics. In contrast to other specialized cell connections such as adherens, gap junctions, and desmosomes, TJs form an uninterrupted intercellular contact at the apical-most end of the lateral side of epithelial cells. Compared to other junctions TJs are made up of different proteins, including claudins, which form the distinctive network of interconnected strands; the multi-PDZ proteins ZO-1, ZO-2, ZO-3, MAGI-1, PatJ, MUPP1, and PALS1, which are interconnected with the transmembrane claudin proteins and are hypothesized to cluster the barrier-forming proteins and enable redundant attachments to the actin cytoskeleton. Disruption of TJ barriers results in the deregulated passage of materials and toxins through the epithelia contributing to a vast array of pathologies. In addition, TJs of endothelial and epithelial cells act as a hub for signaling pathways that determine the proliferative and metastatic ability in cancers. Claudins' function in cancer signaling has been significantly researched. Numerous proof-of-principle studies targeting certain claudins for chemotherapy have been conducted due to the massive overexpression of particular claudins in distinct cancer types.

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Acknowledgment

This study was supported by Ramalingaswami Re-entry Fellowship (Grant number: D.O. NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi and Core Research Grant (CRG/2021/003805) from Science and Engineering Research Board (SERB), Govt. of India, New Delhi to Muzafar A. Macha and Promotion of University Research and Scientific Excellence (PURSE) Grant to the Islamic University of Science and Technology, Awantipora from Department of Biotechnology, Govt. of India. The authors would also like to acknowledge Sidra Medicine Precision Program for funding and constant support to Ajaz A. Bhat and Ammira S.Al-shabeeb Akil.

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Authors and Affiliations

  1. Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Awantipora, Jammu and Kashmir, India

    Sana Khurshid & Muzafar A. Macha

  2. Department of Zoology, School of Life Sciences, Central University of Kashmir, Ganderbal, Jammu and Kashmir, India

    Burhan UlHaq

  3. Department of Microbiology, Sher-I-Kashmir Institute of Medical Science (SKIMS), Soura, Jammu and Kashmir, India

    Sadaf Khursheed

  4. Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, Qatar

    Hana Q. Sadida, Ammira S. Al-Shabeeb Akil & Ajaz A. Bhat

  5. Laboratory of Cancer Immunology and Genetics, Sidra Medicine, Doha, Qatar

    Tariq Masoodi

  6. Department of Medical Oncology, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India

    Mayank Singh

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  1. Sana Khurshid
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Editors and Affiliations

  1. Department of Human Genetics-Precision Medicine in Diabetes, Obesity and Cancer Research Program, Sidra Medicine, Doha, Qatar

    Ajaz A. Bhat

  2. Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Mohammad Haris

  3. Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Jammu and Kashmir, India

    Muzafar A. Macha

  4. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA

    Punita Dhawan

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Khurshid, S. et al. (2023). Tight Junctions and Signaling Pathways in Cancer. In: Bhat, A.A., Haris, M., Macha, M.A., Dhawan, P. (eds) Tight Junctions in Inflammation and Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-99-2415-8_6

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