PXD021604

PXD021604 is an original dataset announced via ProteomeXchange.

Title	Cellular States Dictate Adaptive Signaling Responses to KRASG12C Inhibition: Tyrosine Phosphorylation
Description	Covalent inhibitors of KRASG12C (KRASi) hold considerable progress for tumors driven by this oncogene yet early studies suggest rapid mechanisms of adaptive resistance that appear cell type dependent. To address these challenges, we performed mass spsectrometry baesd phosphoproteomics analysis in KRASG12C cell lines after short term treatment with ARS-1620 and compared phosphoproteomes of KRASG12C cells to understand signaling diversity. Our analysis suggests individual KRASG12C cells responds uniquely to perturbation of KRASG12C. Cell line models can be categorized in epithelial or mesenchymal subtypes and a similar pattern was observed in KRASG12C human lung cancer tumor tissues. ERBB2/3 signaling compensate for repressed ERK signaling following ARS-1620 treatment in epithelial cell type, and this subtype was also more responsive to inhibition of SHP2, IGFR, and SOS1. Conversely, FGFR signaling drives resistance to KRASi in mesenchymal cells in part via mTOR signaling. These studies suggest transcriptional subtypes of KRASG12C dictate responsiveness to specific combinations.
HostingRepository	PRIDE
AnnounceDate	2021-02-16
AnnouncementXML	Submission_2021-02-16_06:07:18.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021604
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-22 01:59:04	ID requested
1	2021-02-15 08:08:42	announced
⏵ 2	2021-02-16 06:07:18	announced	2021-02-16: Updated project metadata.

Dataset with its publication pending

submitter keyword: Lung Cancer, KRAS, phosphoproteomics, mass spectrometry, receptor tyrosine kinases (RTK), targeted therapy, drug resistance, signal transduction

Eric Haura, MD
contact affiliation	Thoracic Oncology
contact email	eric.haura@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021604
     1. Label: PRIDE project
     2. Name: Cellular States Dictate Adaptive Signaling Responses to KRASG12C Inhibition: Tyrosine Phosphorylation