Project summary

The main aim of our project is to identify the role of ASPH in tumors of head and neck, which serves as a model for comparison of the tumors of the same anatomical location with different etiology, in normoxic and hypoxic conditions. One of the partial aims is the identification of the genes influenced by ASPH expression. It allows to identify unknown targets and mechanisms through which ASPH contributes to the malignant phenotype of the cells. Human ASPH catalyzes post-translational hydroxylation of aspartyl and asparaginyl residues in domain resembling epidermal growth factor (EGF). ASPH is important for migration and invasiveness of cells in the natural conditions (trophoblast of placenta) but also in tumors. It has been discovered that one of the mechanisms by which ASPH influences the motility of cells is activation of the Notch signaling pathway. The increase of migration and invasiveness of cells in response to the increased production of ASPH leads to the degradation of extracellular matrix. However, the principal mechanisms of these processes were not described yet. Furthermore, the EGF-like domain is also contained in a number of other proteins besides Notch and nothing is known about the influence of ASPH on their activity. Therefore, we will focus on identification of genes influenced by ASPH expression in normal and immortalized keratinocytes. Additionally, also genes whose expression is influenced by ASPH will be identified in cell lines derived from head and neck tumors of different etiology.

Five relevant publications of the research group

Vojtechova Z, Sabol I, Salakova M, Turek L, Grega M, Smahelova J, Vencalek O, Lukesova E, Klozar J, Tachezy R. Analysis of the integration of human papillomaviruses in head and neck tumours in relation to patients' prognosis. Int J Cancer, 138, 2, 2016. IF 6,513

Koslabova E, Hamsikova E, Salakova M, Klozar J, Foltynova E, Salkova E, Rotnaglova E, Ludvikova V, Tachezy R. Markers of HPV infection and survival in patients with head and neck tumors. Int J Cancer, 133, 8, 1832-9, 2013. IF 6,513

Rotnaglova E, Tachezy R, Salakova M, Prochazka B, Koslabova E, Vesela E, Ludvikova V, Hamsikova E, Klozar J. HPV infection in tonsillar cancer: prognostic significance and clinically relevant markers. Int J Cancer, 129, 1, 101-110, 2011. IF 6,513

Klug SJ, Ressing M, Koenig J, Abba MC, Agorastos T, Brenna SM, Ciotti M, Das BR, Del Mistro A, Dybikowska A, Giuliano AR, Gudleviciene Z, Gyllensten U, Haws AL, Helland A, Herrington CS, Hildesheim A, Humbey O, Jee SH, Kim JW, Madeleine MM, Menczer J, Ngan HY, Nishikawa A, Niwa Y, Pegoraro R, Pillai MR, Ranzani G, Rezza G, Rosenthal AN, Roychoudhury S, Saranath D, Schmitt VM, Sengupta S, Settheetham-Ishida W, Shirasawa H, Snijders PJ, Stoler MH, Suarez-Rincon AE, Szarka K, Tachezy R, Ueda M, van der Zee AG, von Knebel Doeberitz M, Wu MT, Yamashita T, Zehbe I, Blettner M. TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol, 10, 8, 772-784, 2009. IF 33,9

Ho GY, Burk RD, Klein S, Kadish AS, Chang CJ, Palan P, Basu J, Tachezy R, Lewis R, Romney S. Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia. J Natl Cancer Inst, 87, 18, 1365-1371, 1995. IF 13,757

Current research grants of the group

Phenotype and function of head and neck squamous carcinoma immune cells as predictive markers of clinical response, 2017-2022, AZV 17-28255A

The role of aspartyl beta-hydroxylase in tumors associated and non-associated with human papillomaviruses, 2019-2022, Inter-Excellence, sub-program Inter-Action LTAUSA18003

Center for Tumor Ecology – Research of the Cancer Microenvironment Supporting Cancer Growth and Spread, 2018-2023, Excellent Research, MŠMT CZ.02.1.01/0.0/0.0/16_019/0000785

Metagenomic analysis of the virome of the honeybee (Apis mellifera) in the Czech Republic, 2017-2019, CELSA (Central Europe Leuven Strategic Alliance)

The development of MULTIOMICS pesticide risk assessment for bees with regard to real contamination and other stressors, 2019-2023, QK – Program of applied research Ministry of agriculture, Earth, QK1910018

Source of financial support of the project
(min. 5000 CZK per month)

The role of aspartyl beta-hydroxylase in tumors associated and non-associated with human papillomaviruses, 2019-2022, Inter-Excellence, sub-program Inter-Action LTAUSA18003

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