PXD000861

PXD000861 is an original dataset announced via ProteomeXchange.

Title	Phosphopattern Predicts CK2 Substrate, HMGA1, as a Drug Resistant Target for Non-Small Cell Lung Cancer
Description	Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs), including gefitinib. Acquired resistance to EGFR-TKIs develops after prolonged treatments. Known mechanisms for EGFR-TKI resistance, including KRAS mutation, HER2 mutation, EGFR T790M mutation and MET gene amplification did not observe in the resistant cells, PC9/gef. The study was prompt to explore effective strategies against resistance to EGFR-TKIs in PC9/gef cells. Here, we used label-free quantitative mass spectrometry to globally profile the basal phosphoproteome and proteome of a panel of TKI sensitive PC9, TKI resistant PC9/gef and TKI dose-dependent PC9/gef NSCLC cell lines. For phosphorylation level, we identified 5844 phosphorylation sites from 4612 phosphopeptides of 1548 proteins. For protein level, we identified 3835 proteins. Most of the quantitatively change is from phosphorylation whereas most of the protein level is unchanged. Among these big datasets, there is a phosphopattern of phosphopeptides presented up-regulated in resistant cells but no response to further gefitinib treatment; we proposed this group could regulate drug resistance. By motif analysis, these phosphopeptides mapped to the corresponding kinases, CK2, as the drug resistant kinase. Network analysis showed that CK2 directed interacting with 10 proteins. Among these proteins, we found that HMGA1 is the substrate protein to CK2. By biochemical evidence, we discovered that CK2 could regulate cell death in TKI-resistant cells. Furthermore, we found that HMGA1 for the first time could be the potential drug resistant target to reverse the drug resistance in PC9/gef cells. The results provide new insights into HMGA1 as the drug resistant target through the cellular signaling networks associated with the TKI-induced drug resistant NSCLCs.
HostingRepository	PRIDE
AnnounceDate	2018-05-08
AnnouncementXML	Submission_2018-05-08_00:33:35.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD000861
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Chia-Feng Tsai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2014-03-27 07:29:21	ID requested
⏵ 1	2018-05-08 00:33:36	announced

Wang YT, Pan SH, Tsai CF, Kuo TC, Hsu YL, Yen HY, Choong WK, Wu HY, Liao YC, Hong TM, Sung TY, Yang PC, Chen YJ, Phosphoproteomics Reveals HMGA1, a CK2 Substrate, as a Drug-Resistant Target in Non-Small Cell Lung Cancer. Sci Rep, 7():44021(2017) [pubmed]

submitter keyword: CK2, HMGA1, Drug resistance, IMAC, phosphoproteome, lung cancer

Yu-Ju Chen
contact affiliation	Institute of Chemistry, Academia Sinica, Taipei, Taiwan
contact email	yujuchen@gate.sinica.edu.tw
lab head
Chia-Feng Tsai
contact affiliation	Institute of Chemistry
contact email	grazzilybear@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/05/PXD000861

PRIDE project URI

• PRIDE
  1. PXD000861
     1. Label: PRIDE project
     2. Name: Phosphopattern Predicts CK2 Substrate, HMGA1, as a Drug Resistant Target for Non-Small Cell Lung Cancer