PXD026557 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteomic and phosphoproteomics profiling depict drug addiction mechanisms in BRAFi-resistant melanoma |
Description | Acquired resistance to MAPK inhibitors limits the clinical efficacy in melanoma treatment. We and others have recently shown that BRAF inhibitors (BRAFi)-resistant melanoma cells can develop a dependency on the therapeutic drugs to which they have acquired resistance, creating a vulnerability for these cells that can potentially be exploited in cancer treatment. In drug addicted melanoma cells, it was shown that this induction of cell death was preceded by a specific ERK2-dependent phenotype switch, however, the underlying molecular mechanisms are largely lacking. To increase the molecular understanding of this drug dependency, we applied a mass spectrometry-based proteomic approach on BRAFi-resistant BRAFMUT 451Lu cells, in which ERK1, ERK2 and JUNB were silenced separately using CRISPR–Cas9. Inactivation of ERK2 and, to a lesser extent, JUNB prevents drug addiction in these melanoma cell while, conversely, knock out of ERK1 fails to reverse this phenotype, showing a response similar to control cells. Our analysis reveals that ERK2 and JUNB share comparable proteome responses dominated by reactivation of cell division. Importantly, we find that EMT activation in drug addicted melanoma cells upon drug withdrawal is affected by silencing ERK2 but not ERK1. Moreover, transcription factor (regulator) enrichment shows that PIR acts as an effector of ERK2 and phosphoproteome analysis reveals that silencing of ERK2 but not ERK1 leads to amplification of GSK3 kinase activity. Our results depict possible mechanisms of drug addiction in melanoma, which may provide a guide for strategies in drug-resistant melanoma. |
HostingRepository | PRIDE |
AnnounceDate | 2022-02-17 |
AnnouncementXML | Submission_2022-02-17_09:14:47.095.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Bohui Li |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-06-07 22:56:42 | ID requested | |
⏵ 1 | 2022-02-17 09:14:47 | announced | |
Publication List
Li B, Kong X, Post H, Raaijmakers L, Peeper DS, Altelaar M, Proteomics and Phosphoproteomics Profiling of Drug-Addicted BRAFi-Resistant Melanoma Cells. J Proteome Res, 20(9):4381-4392(2021) [pubmed] |
Keyword List
submitter keyword: Melanoma |
BRAF resistant |
Proteomics |
Phosphoproteomics |
ERK2/MAPK1 |
ERK1/MAPK3 |
EMT |
Contact List
Maarten Altelaar |
contact affiliation | 1 Biomolecular Mass Spectrometry and Proteomics Group, Utrecht Institute for Pharmaceutical Science, Utrecht University, Utrecht, The Netherlands. 2 Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, The Netherlands 3 Mass Spectrometry and Proteomics Facility, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands |
contact email | m.altelaar@uu.nl |
lab head | |
Bohui Li |
contact affiliation | Biomolecular Mass Spectrometry and Proteomics Group, Utrecht Institute for Pharmaceutical Science, Utrecht University, Utrecht, The Netherlands. |
contact email | libohui123@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD026557
- Label: PRIDE project
- Name: Proteomic and phosphoproteomics profiling depict drug addiction mechanisms in BRAFi-resistant melanoma