PXD006705 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
Solanki HS, Raja R, Zhavoronkov A, Ozerov IV, Artemov AV, Advani J, Radhakrishnan A, Babu N, Puttamallesh VN, Syed N, Nanjappa V, Subbannayya T, Sahasrabuddhe NA, Patil AH, Prasad TSK, Gaykalova D, Chang X, Sathyendran R, Mathur PP, Rangarajan A, Sidransky D, Pandey A, Izumchenko E, Gowda H, Chatterjee A, Targeting focal adhesion kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of epidermal growth factor receptor. Oncoscience, 5(1-2):21-38(2018) [pubmed] |
10.18632/oncoscience.395; |
Keyword List
submitter keyword: epidermal growth factor receptor, drug resistance, NSCLC,cigarette smoke, phosphoproteomics |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD006705
- Label: PRIDE project
- Name: Targeting Focal Adhesion Kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of Epidermal Growth Factor Receptor