PXD033921

PXD033921 is an original dataset announced via ProteomeXchange.

Title	Effect of PTEN knockout on dabrafenib-trametinib treatment in A375 melanoma cells - replicate 2
Description	Approximately 50% of melanomas harbor an activating BRAFV600E mutation. Standard of care involves a combination of inhibitors targeting mutant BRAF and MEK1/2, the substrate for BRAF in the MAPK pathway. PTEN loss of function mutations occur in 40% of BRAFV600E melanomas, resulting in increased PI3K/AKT activity that enhances resistance to BRAF/MEK combination inhibitor therapy. To compare the response of PTEN null to PTEN wild type cells in an isogenic background, CRISPR was used to knock out PTEN in the A375 melanoma cell line that harbors a BRAFV600E mutation. Kinome profiling was performed using the parental line and two PTEN KO clones (5 and 11), treated with DMSO, or treated with 100nM dabrafenib and 10nM trametinib for 1 day or for 7 days. PTEN KO cells showed dramatically increased binding of HER3 and AKT3 compared to wild type. The activation of the SOX10-FOXD3-HER3-AKT axis in PTEN KO cells could be targeted with the ERBB/HER inhibitor neratinib.
HostingRepository	PRIDE
AnnounceDate	2024-04-23
AnnouncementXML	Submission_2024-04-23_06:11:30.342.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Steven Angus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-16 08:25:16	ID requested
⏵ 1	2024-04-23 06:11:30	announced

Dataset with its publication pending

submitter keyword: A375, kinase inhibitor, BRAF,melanoma, MEK, kinome

Steven Angus
contact affiliation	Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202
contact email	sangus@iu.edu
lab head
Steven Angus
contact affiliation	Indiana University School of Medicine
contact email	sangus@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033921
     1. Label: PRIDE project
     2. Name: Effect of PTEN knockout on dabrafenib-trametinib treatment in A375 melanoma cells - replicate 2