SIRT2 Contributes to the Resistance of Melanoma Cells to the Multikinase Inhibitor Dasatinib

Autorzy publikacji z podkreśleniem autorów z projektu Karwaciak I., Sałkowska A., Karaś K., Sobalska-Kwapis M., Walczak-Drzewiecka A., Pułaski Ł., Strapagiel D., Dastych J., Ratajewski M.
Nazwa czasopisma Cancers (Basel)
Rok publikacji 2019
IF czasopisma w czasie publikacji pracy 4,246
Punkty MNiSW w czasie publikacji pracy 140
Streszczenie w j. angielskim lub krótki opis pracy 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.


Link do publikacji SIRT2 Contributes to the Resistance of Melanoma Cells to the Multikinase Inhibitor Dasatinib


DOI 10.3390/cancers11050673
Michał Osiński

Autor:Michał Osiński

Senior Specialist