Compagnone, M. et al. (2017) ΔNp63-mediated regulation of hyaluronic acid metabolism and signaling supports HNSCC tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America, 114(50), pp. 13254-13259. (doi: 10.1073/pnas.1711777114) (PMID:29162693) (PMCID:PMC5740608)
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152889.pdf - Accepted Version 1MB |
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and several molecular pathways that underlie the molecular tumorigenesis of HNSCC have been identified. Among them, amplification or overexpression of ΔNp63 isoforms is observed in the majority of HNSCCs. Here, we unveiled a ΔNp63-dependent transcriptional program able to regulate the metabolism and the signaling of hyaluronic acid (HA), the major component of the extracellular matrix (ECM). We found that ∆Np63 is capable of sustaining the production of HA levels in cell culture and in vivo by regulating the expression of the HA synthase HAS3 and two hyaluronidase genes, HYAL-1 and HYAL-3. In addition, ∆Np63 directly regulates the expression of CD44, the major HA cell membrane receptor. By controlling this transcriptional program, ∆Np63 sustains the epithelial growth factor receptor (EGF-R) activation and the expression of ABCC1 multidrug transporter gene, thus contributing to tumor cell proliferation and chemoresistance. Importantly, p63 expression is positively correlated with CD44, HAS3, and ABCC1 expression in squamous cell carcinoma datasets and p63-HA pathway is a negative prognostic factor of HNSCC patient survival. Altogether, our data shed light on a ∆Np63-dependent pathway functionally important to the regulation of HNSCC progression.
| Item Type: | Articles |
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| Keywords: | HNSCC, hyaluronic acid, p63. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Markert, Dr Elke |
| Authors: | Compagnone, M., Gatti, V., Presutti, D., Ruberti, G., Fierro, C., Markert, E. K., Vousden, K. H., Zhou, H., Mauriello, A., Anemone, L., Bongiorno-Borbone, L., Melino, G., and Peschiaroli, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Published Online: | 21 November 2017 |
| First Published: | First published in Proceedings of the National Academy of Sciences of the United States of America 114(50): 13254-13259 |
| Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
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