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Czerniak złośliwy jest najbardziej agresywnym rakiem skóry i można go wyleczyć tylko wtedy, gdy zostanie wykryty na wczesnym etapie. Niestety, późniejsze stadia choroby nie gwarantują sukcesu ze względu na szybkie tempo przerzutów komórek czerniaka i ich wysoką odporność na zastosowane terapie. Naukowcy z Instytutu Biologii Medycznej Polskiej Akademii Nauk przy współpracy z Pracownią Biobank Uniwersytetu Łódzkiego podjęli badania mające na celu sprawdzenie roli genu SIRT2 w komórkach czerniaka. Wyniki swojej pracy przedstawili w artykule “SIRT2 Contributes to the Resistance of Melanoma Cells to the Multikinase Inhibitor Dasatinib” opublikowanym na łamach Cancers (IF=5.326). Zapraszamy do lektury.

 

 

 

Iwona Karwaciak 1,Anna Sałkowska 2,Kaja Karaś 2,Marta Sobalska-Kwapis 3,4,Aurelia Walczak-Drzewiecka 5,Łukasz Pułaski 1,Dominik Strapagiel 3,4,Jarosław Dastych 5 andMarcin Ratajewski 2

 

1Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
2Laboratory of Epigenetics, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
3Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland
4BBMRI.pl Consortium, 54-066 Wroclaw, Poland
5Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland

 

Abstract

Malignant melanoma is the most aggressive skin cancer and can only be cured if detected early. Unfortunately, later stages of the disease do not guarantee success due to the rapid rate of melanoma cell metastasis and their high resistance to applied therapies. The search for new molecular targets and targeted therapy may represent the future in the development of effective methods for combating this cancer. SIRT2 is a promising target; thus, we downregulated SIRT2 expression in melanoma cells in vertical growth and metastatic phases and demonstrated that sirtuin acts as regulator of the basic functions of melanoma cells. A detailed transcriptomic analysis showed that SIRT2 regulates the expression of multiple genes encoding the tyrosine kinase pathways that are molecular targets of dasatinib. Indeed, cells with low SIRT2 expression were more susceptible to dasatinib, as demonstrated by multiple techniques, e.g., neutral red uptake, 3/7 caspase activity, colony formation assay, and in vitro scratch assay. Furthermore, these cells showed an altered phosphorylation profile for proteins playing roles in the response to dasatinib. Thus, our research indicates new, previously unknown SIRT2 functions in the regulation of gene expression, which is of key clinical significance.