PXD006705

PXD006705 is an original dataset announced via ProteomeXchange.

Title	Targeting Focal Adhesion Kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of Epidermal Growth Factor Receptor
Description	Cigarette smoking is the leading cause for non-small cell lung carcinoma (NSCLC). Tyrosine kinase inhibitors (TKIs) targeting EGFR are in clinical practice and has benefitted patients with EGFR mutations. However, EGFR based targeted therapies have shown limited success in smokers. Identification of alternate signaling mechanism(s) leading to TKI resistance in smokers is critical for developing novel therapies for lung cancer. We observed increased resistance to erlotinib in H358 lung cancer cells exposed to cigarette smoke (H358-S) compared to parental cells. To systematically identify signaling pathways that could potentially confer resistance to erlotinib, we carried out stable isotope labeling by amino acids in cell culture (SILAC)-based phosphotyrosine analysis of H358-S and parental cells. We identified 238 unique phosphosites, of which 111 phosphosites were hyperphosphorylated (≥ 2-fold¬¬¬¬¬¬) in H358 -S cells. Importantly, we observed hyperphosphorylation of EGFR at Y1197 and non-receptor tyrosine kinases, including FAK and FRK in H358-S cells. Inhibition of FAK with its inhibitor PF-562271 led to decreased cellular proliferation and invasive ability of the smoke exposed cells. Further, we observed that treatment with PF-562271 could restore dependency of H358-S cells on EGFR signaling.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:38:36.984.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aditi Chatterjee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; 6x(13)C labeled residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-06-13 06:32:23	ID requested
1	2018-03-21 01:26:12	announced
⏵ 2	2024-10-22 04:38:45	announced	2024-10-22: Updated project metadata.

10.18632/oncoscience.395;

submitter keyword: epidermal growth factor receptor, drug resistance, NSCLC,cigarette smoke, phosphoproteomics

Aditi Chatterjee
contact affiliation	Institute of Bioinformatics, Bangalore, Karnataka, India
contact email	aditixchatterjee@gmail.com
lab head
Aditi Chatterjee
contact affiliation	Institute of Bioinformatics, Bangalore, Karnataka, India
contact email	aditixchatterjee@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006705
     1. Label: PRIDE project
     2. Name: Targeting Focal Adhesion Kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of Epidermal Growth Factor Receptor