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Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications

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Abstract

Background

Oral squamous cell carcinoma (OSCC) is a malignant oral cavity neoplasm that affects many people, especially in developing countries. Despite several advances that have been made in diagnosis and treatment, the morbidity and mortality rates due to OSCC remain high. Accumulating evidence indicates that aberrant activation of cellular signaling pathways, such as the Notch, Wnt and Hedgehog pathways, occurs during the development and metastasis of OSCC. In this review, we have articulated the roles of the Notch, Wnt and Hedgehog signaling pathways in OSCC and their crosstalk during tumor development and progression. We have also examined possible interactions and associations between these pathways and treatment regimens that could be employed to effectively tackle OSCC and/or prevent its recurrence.

Conclusions

Activation of the Notch signaling pathway upregulates the expression of several genes, including c-Myc, β-catenin, NF-κB and Shh. Associations between the Notch signaling pathway and other pathways have been shown to enhance OSCC tumor aggressiveness. Crosstalk between these pathways supports the maintenance of cancer stem cells (CSCs) and regulates OSCC cell motility. Thus, application of compounds that block these pathways may be a valid strategy to treat OSCC. Such compounds have already been employed in other types of cancer and could be repurposed for OSCC.

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Acknowledgements

Work on OSCC Notch signaling has been performed in the lab through an Indo-Africa project sanctioned by the Government of India. The authors thank the Department of Science and Technology (DST), Government of India, for the support.

Funding

Funded through an Indo South Africa project sanctioned by the Department of Science and Technology (DST), Government of India, under the Bilateral Programme (DST/INT/SOUTH Africa/P-12/2016).

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  1. Anjali P. Patni, M. K. Harishankar and Joel P. Joseph contributed equally to this work.

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  1. Stem Cell Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kanchipuram, Kattankulathur, Chennai, Tamil Nadu, 603203, India

    Anjali P. Patni, M. K. Harishankar, Joel P. Joseph, Bhuvanadas Sreeshma & Arikketh Devi

  2. College of Human and Human Sciences, Charles Darwin University, Ellangowan Drive, Darwin, Northern Territory, 0909, Australia

    Rama Jayaraj

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Patni, A.P., Harishankar, M.K., Joseph, J.P. et al. Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications. Cell Oncol. 44, 473–494 (2021). https://doi.org/10.1007/s13402-021-00591-3

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