-
Inhibition of stearoyl-CoA desaturase 1 reverts BRAF and MEK inhibition-induced selection of cancer stem cells in BRAF-mutated melanoma [Elektronski vir]Pisanu, Maria Elena ...Background Combination therapy with BRAF and MEK inhibitors significantly improves survival in BRAF mutated melanoma patients but is unable to prevent disease recurrence due to the emergence of drug ... resistance. Cancer stem cells (CSCs) have been involved in these long-term treatment failures. We previously reported in lung cancer that CSCs maintenance is due to altered lipid metabolism and dependent upon Stearoyl-CoA-desaturase (SCD1)-mediated upregulation of YAP and TAZ. On this ground, we investigated the role of SCD1 in melanoma CSCs. Methods SCD1 gene expression data of melanoma patients were downloaded from TCGA and correlated with disease progression by bioinformatics analysis and confirmed on patient%s tissues by qRT-PCR and IHC analyses. The effects of combination of BRAF/MEKi and the SCD1 inhibitor MF-438 were monitored by spheroid-forming and proliferation assays on a panel of BRAF-mutated melanoma cell lines grown in 3D and 2D conditions, respectively. SCD1, YAP/TAZ and stemness markers were evaluated in melanoma cells and tissues by qRT-PCR, WB and Immunofluorescence. Results We first observed that SCD1 expression increases during melanoma progression. BRAF-mutated melanoma 3D cultures enriched for CSCs overexpressed SCD1 and were more resistant than 2D differentiated cultures to BRAF and MEK inhibitors. We next showed that exposure of BRAF-mutated melanoma cells to MAPK pathway inhibitors enhanced stemness features by upregulating the expression of YAP/TAZ and downstream genes but surprisingly not SCD1. However, SCD1 pharmacological inhibition was able to downregulate YAP/TAZ and to revert at the same time CSC enrichment and resistance to MAPK inhibitors. Conclusions Our data underscore the role of SCD1 as prognostic marker in melanoma and promote the use of SCD1 inhibitors in combination with MAPK inhibitors for the control of drug resistance.Source: Journal of experimental & clinical cancer research [Elektronski vir]. - ISSN 1756-9966 (Vol. 37, 2018, str. 1-17)Type of material - e-articlePublish date - 2018Language - englishCOBISS.SI-ID - 4650353
Author
Pisanu, Maria Elena |
Maugeri-Saccà, Marcello |
Fattore, Luigi |
Bruschini, Sara |
Vitis De, Claudia |
Tabbì, Eugenio |
Bellei, Barbara |
Migliano, Emilia |
Kovacs, Daniela |
Camera, Emanuela |
Picardo, Mauro |
Jakopin, Žiga
Topics
Melanoma |
Genetics |
Melanom |
Matične celice |
metabolizem lipidov |
BRAF zaviralci |
MEK zaviralci |
lipid metabolism |
Melanoma cancer stem cells |
BRAF |
MEK inhibitors
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|---|
Pisanu, Maria Elena | ![]() |
Maugeri-Saccà, Marcello | ![]() |
Fattore, Luigi | ![]() |
Bruschini, Sara | ![]() |
Vitis De, Claudia | ![]() |
Tabbì, Eugenio | ![]() |
Bellei, Barbara | ![]() |
Migliano, Emilia | ![]() |
Kovacs, Daniela | ![]() |
Camera, Emanuela | ![]() |
Picardo, Mauro | ![]() |
Jakopin, Žiga | 26496 |
Select pickup location:
Material pickup by post
Notification
Subject headings in COBISS General List of Subject Headings
Select pickup location
Pickup location | Material status | Reservation |
---|
Please wait a moment.