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The mechanism of the contribution of ICAM-1 to epithelial–mesenchymal transition (EMT) in bladder cancer

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Abstract

Bladder cancer is one of the most prevalent cancers worldwide. Moreover, if not optimally treated, bladder cancer is a significant burden on healthcare systems due to multiple recurrences which often require more aggressive therapies. Therefore, targeted anti-cancer therapies, developed based on an in-depth understanding of specific proteins and molecular mechanisms, are promising in cancer treatment. Here, for the first time, we presented the new approaches indicating that intracellular adhesion molecule-1 (ICAM-1) may play a potential role in enhancing therapeutic effectiveness for bladder cancer. In the present study, we presented that ICAM-1 expression as well as its regulation in bladder cancer is strongly correlated with the high expression of N-cadherin. Importantly, the presence of N-cadherin and its regulator—TWIST-1 was abolished when ICAM-1 was silenced. We identified also that ICAM-1 is capable of regulating cellular migration, proliferation, and EMT progression in bladder cancer cells via the N-cadherin/SRC/AKT/GSK-3β/β-catenin signaling axis. Therefore, we propose ICAM-1 as a novel metastatic marker for EMT progression, which may also be used as a therapeutic target in bladder cancer.

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Acknowledgements

This work was supported by the National Science Centre (NCN, Poland, grant no. 2020/04/X/NZ5/00724) and by a grant from Science & Higher Education (MNiSW) through the Jagiellonian University Medical College N41/DBS/000943. The purchase of a microplate reader (BioKom Synergy, HTX) has been supported by a grant from the Priority Research Area qLIFE under the Strategic Programme Excellence Initiative at Jagiellonian University in Kraków. Poland.

Funding

This work was supported by the National Science Centre (NCN, Poland, grant no. 2020/04/X/NZ5/00724) and by a grant from Science & Higher Education (MNiSW) through the Jagiellonian University Medical College N41/DBS/000943. The purchase of a microplate reader (BioKom Synergy, HTX) has been supported by a grant from the Priority Research Area qLIFE under the Strategic Programme Excellence Initiative at Jagiellonian University in Kraków. Poland.

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Authors and Affiliations

  1. Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, 31-034, Kraków, Poland

    Marta Zarzycka & Dorota Gil

  2. Department of Animal Anatomy and Preclinical Sciences, University Centre of Veterinary Medicine JU-UA, University of Agriculture in Kraków, Mickiewicza 24/28, 30-059, Kraków, Poland

    Małgorzata Kotula-Balak

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  1. Marta Zarzycka
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Contributions

M.Z. conceived the original idea, designed the study, performed the experiments, performed the figures and graphical abstract, performed statistical analysis of data, and wrote the manuscript; M.K-B. reviewed and edited the manuscript; D.G. performed proliferation analysis, helped with siRNA transfection, and reviewed and edited the manuscript. All authors have read and approved the final version of the manuscript.

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Correspondence to Marta Zarzycka.

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Zarzycka, M., Kotula-Balak, M. & Gil, D. The mechanism of the contribution of ICAM-1 to epithelial–mesenchymal transition (EMT) in bladder cancer. Human Cell 37, 801–816 (2024). https://doi.org/10.1007/s13577-024-01053-2

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