Next Article in Journal
CAR T-Cells Targeting the Integrin αvβ6 and Co-Expressing the Chemokine Receptor CXCR2 Demonstrate Enhanced Homing and Efficacy against Several Solid Malignancies
Previous Article in Journal
Oligodeoxynucleotides ODN 2006 and M362 Exert Potent Adjuvant Effect through TLR-9/-6 Synergy to Exaggerate Mammaglobin-A Peptide Specific Cytotoxic CD8+T Lymphocyte Responses against Breast Cancer Cells
Previous Article in Special Issue
Palliative Electrochemotherapy in Vulvar Carcinoma: Preliminary Results of the ELECHTRA (Electrochemotherapy Vulvar Cancer) Multicenter Study
Article Menu

Export Article

Open AccessArticle

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

1
Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
2
Laboratory of Epigenetics, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
3
Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland
4
BBMRI.pl Consortium, 54-066 Wroclaw, Poland
5
Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 673; https://doi.org/10.3390/cancers11050673
Received: 5 April 2019 / Revised: 8 May 2019 / Accepted: 12 May 2019 / Published: 14 May 2019
(This article belongs to the Collection Drug Resistance and Novel Therapies in Cancers)
PDF [15692 KB, uploaded 14 May 2019]

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.
Keywords: melanoma, SIRT2, sirtuins, tyrosine kinase, resistance melanoma, SIRT2, sirtuins, tyrosine kinase, resistance
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Karwaciak, I.; Sałkowska, A.; Karaś, K.; Sobalska-Kwapis, M.; Walczak-Drzewiecka, A.; Pułaski, Ł.; Strapagiel, D.; Dastych, J.; Ratajewski, M. SIRT2 Contributes to the Resistance of Melanoma Cells to the Multikinase Inhibitor Dasatinib. Cancers 2019, 11, 673.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top