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| Status |
Public on Nov 18, 2015 |
| Title |
Trascriptional profile of BRAF inhibitor-resistant SKMEL28 and WM3248 melanoma cells and changes upon YAP/TAZ siRNA knockdown |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The activation of transcriptional coactivators YAP and its paralog TAZ has been shown to promote resistance to anti-cancer therapies. YAP/TAZ activity is tightly coupled to actin cytoskeleton architecture. However, the influence of actin remodeling on cancer drug resistance remains largely unexplored. Here, we report a pivotal role of actin remodeling in YAP/TAZ-dependent BRAF inhibitor resistance in BRAF V600E mutant melanoma cells. Melanoma cells resistant to BRAF inhibitor PLX4032 exhibit an increase in actin stress fiber formation, which appears to promote the nuclear accumulation of YAP/TAZ. Knockdown of YAP/TAZ overcomes PLX4032 resistance, whereas overexpression of constitutively active YAP induces resistance. Moreover, inhibition of actin polymerization and cytoskeletal tension in melanoma cells suppresses both YAP/TAZ activation and PLX4032 resistance. Our siRNA library screening identifies actin dynamics regulator TESK1 as a novel vulnerable point of the YAP/TAZ-dependent resistance pathway. These results suggest that inhibition of actin remodeling is a promising synthetic lethal strategy to suppress resistance in BRAF inhibitor therapies.
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| Overall design |
We compared expression profile of PLX4032 resistant SKMEL28 and WM3248 melanoma cells to parental cells (two biologic replicates each). We also compared expression profile changes from two biologic replicates of PLX4032-resistant SKMEL28 and WM3248 cells transfected with either control siRNA or YAP/TAZ siRNAs for 72 hrs
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| Contributor(s) |
Kim M, Kim J, Hong H, Lee S, Lee J, Jung E, Kim J |
| Citation(s) |
26668268 |
| Submission date |
May 06, 2015 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Min Hwan Kim |
| E-mail(s) |
gemgoon3691@gmail.com
|
| Phone |
82-010-8285-3691
|
| Organization name |
KAIST
|
| Department |
Graduate School of Medical Science and Engineering
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| Lab |
Disease Functional Genomics Lab
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| Street address |
KAIST 291 Daehak-ro, Yuseong-gu
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| City |
Daejeon |
| ZIP/Postal code |
305-338 |
| Country |
South Korea |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA283194 |
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