Identification of cytokeratin24 as a tumor suppressor for the management of head and neck cancer
Author:
Gül Désirée1ORCID, Habtemichael Negusse1, Dietrich Dimo2, Dietrich Jörn2, Gößwein Dorothee1, Khamis Aya1, Deuss Eric13, Künzel Julian4, Schneider Günter4, Strieth Sebastian2, Stauber Roland H.1
Affiliation:
1. Department of Otorhinolaryngology Head and Neck Surgery, Molecular and Cellular Oncology , University Medical Center , D-55131 Mainz , Germany 2. Department of Otorhinolaryngology, University Medical Center Bonn , D-53127 Bonn , Germany 3. Department of Otorhinolaryngology Head and Neck Surgery , University Hospital , D-45147 Essen , Germany 4. Ear, Nose and Throat Department , University Hospital , D-93053 Regensburg , Germany
Abstract
Abstract
To improve management of head and neck squamous cell carcinoma patients, we need to increase our understanding of carcinogenesis, to identify biomarkers, and drug targets. This study aimed to identify novel biomarkers by providing transcriptomics profiles of matched primary tumors, lymph node metastasis, and non-malignant tissue of 20 HNSCC patients as well as by bioinformatic analyses of a TCGA HNSCC cohort, comprising 554 patients. We provide cancer cell signaling networks differentially expressed in tumors versus metastases, such as mesenchymal–epithelial transition, and structural integrity networks. As a proof of principle study, we exploited the data sets and performed functional analyses of a novel cytokeratin, cytokeratin24 (cKRT24), which had not been described as biomarker for tumors before. Survival analysis revealed that low cKRT24 expression correlated with poor overall survival in HNSCC. Experimentally, downregulation of cKRT24 in primary tumors, metastases, and HNSCC cell lines was verified on mRNA and protein level. Cloning and ectopic overexpression of cKRT24 not only affected viability and growth of HNSSC cell lines, but also inhibited tumor growth in murine xenograft studies. We conclude that cKRT24 functions as a tumor suppressor in HNSCC, and may serve as an additional prognostic biomarker and novel target to support current HNSCC treatments.
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
Reference145 articles.
1. Alevizos, I., Mahadevappa, M., Zhang, X., Ohyama, H., Kohno, Y., Posner, M., Gallagher, G.T., Varvares, M., Cohen, D., Kim, D., et al.. (2001). Oral cancer in vivo gene expression profiling assisted by laser capture microdissection and microarray analysis. Oncogene 20: 6196–6204, https://doi.org/10.1038/sj.onc.1204685. 2. Alizadeh, A.A., Eisen, M.B., Davis, R.E., Ma, C., Lossos, I.S., Rosenwald, A., Boldrick, J.C., Sabet, H., Tran, T., Yu, X., et al.. (2000). Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403: 503–511, https://doi.org/10.1038/35000501. 3. Al Moustafa, A.E., Alaoui-Jamali, M.A., Batist, G., Hernandez-Perez, M., Serruya, C., Alpert, L., Black, M.J., Sladek, R., and Foulkes, W.D. (2002). Identification of genes associated with head and neck carcinogenesis by cDNA microarray comparison between matched primary normal epithelial and squamous carcinoma cells. Oncogene 21: 2634–2640, https://doi.org/10.1038/sj.onc.1205351. 4. Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T., et al.. (2000). Gene ontology: tool for the unification of biology. Gene Ontol. Consortium Nat. Genet. 25: 25–29, https://doi.org/10.1038/75556. 5. Aymard, E., Barruche, V., Naves, T., Bordes, S., Closs, B., Verdier, M., and Ratinaud, M.H. (2011). Autophagy in human keratinocytes: an early step of the differentiation? Exp. Dermatol. 20: 263–268, https://doi.org/10.1111/j.1600-0625.2010.01157.x.
Cited by
10 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|