Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Hebesberger, T.
Ahnak the giant protein: expression, localization and functionality in human chordoma cell lines.
[ Diplomarbeit/Master Thesis (UNI) ] University of Graz; 2018. pp.54.
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- Abstract:
- Chordoma is a slow but invasive growing bone tumor, which is considered to be chemo-resistant. So far, no conventional chemotherapy is known that has a significant impact on tumor growth. The protein AHNAK recently gained momentum in cancer researcher, as there are several studies indicating a relation between AHNAK expression level and proliferation, differentiation and migration in various cancer cell lines. Since our own preliminary data indicated high AHNAK expression in chordoma tumor tissue, we aimed to characterize AHNAK in human chordoma cell lines, in terms of expression level, localization and functionality. We thereby wanted to introduce AHNAK as a possible new diagnostic biomarker and/or as a new therapeutic target for chemotherapy. We provide evidence, that mRNA and protein levels of AHNAK vary among chordoma cell lines and among chordoma tumor tissue. Localization studies by immunofluorescence demonstrated mostly cytosolic localization and localization in vicinity to the nucleus. Immunohistochemical staining of two tumor tissue samples indicated that AHNAK is localized mainly on the cell membrane. Upon expression and localization studies we performed viability, cell cycle and cell fate assays in combination with siRNA mediated knockdown of AHNAK. These studies indicated a possible tumor progressive role of AHNAK in chordoma since knockdown resulted in a reduced viability, an accumulation of cells in the G2 phase and an increase in necrotic and necrotic/late apoptotic cells. These results so far reject the use of AHNAK as a diagnostic biomarker but indicate a possible use as prognostic biomarker instead. Results, addressing AHNAKs functionality in chordoma, support a possible future use of AHNAK as a therapeutic target, since a potential tumor progressive role of AHNAK in chordoma could be indicated.