PXD007946

PXD007946 is an original dataset announced via ProteomeXchange.

Title	PIM1 kinase promotes gallbladder cancer cell proliferation via inhibition of proline-rich Akt substrate of 40 kDa (PRAS40)
Description	Gallbladder cancer (GBC) is associated with poor disease prognosis with a survival of less than 5 years in 90% the cases. This has been attributed to late presentation of the disease, lack of early diagnostic markers and limited efficiency of therapeutic interventions. Elucidation of the molecular events in GBC carcinogenesis can contribute in better management of the disease by aiding in identification of therapeutic targets. To identify the aberrantly activated signaling events in GBC, tandem mass tag-based quantitative phosphoproteomic analysis of five GBC cell lines based on the invasive property was carried out. Using a panel of five GBC cell lines, a total of 2,623 phosphosites from 1,343 proteins were identified. Of these, 55 phosphosites were hyperphosphorylated and 39 phosphosites were hypophosphorylated in both replicates and all the 4 invasive GBC cell lines. Proline-rich Akt substrate 40 kDa (PRAS40) was one of the proteins found to be hyperphosphorylated in all the invasive GBC cell lines. Tissue microarray-based immunohistochemical labeling of phospho-PRAS40 (T246) revealed moderate to strong staining in 77% of the primary gallbladder adenocarcinoma cases. Inhibition of PRAS40 phosphorylation using inhibitors of its upstream kinases, PIM1 and AKT resulted in a significant decrease in cell proliferation, colony forming and invasive ability of the GBC cells. Our findings support the role of PRAS40 phosphorylation in tumor cell survival and aggressiveness in GBC and suggest its potential as a therapeutic target for GBC.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:41:40.654.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harsha Gowda
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-11 08:34:18	ID requested
1	2019-01-28 04:08:43	announced
⏵ 2	2024-10-22 04:41:48	announced	2024-10-22: Updated project metadata.

10.1007/s12079-018-00503-5;

Subbannayya T, Leal-Rojas P, Zhavoronkov A, Ozerov IV, Korzinkin M, Babu N, Radhakrishnan A, Chavan S, Raja R, Pinto SM, Patil AH, Barbhuiya MA, Kumar P, Guerrero-Preston R, Navani S, Tiwari PK, Kumar RV, Prasad TSK, Roa JC, Pandey A, Sidransky D, Gowda H, Izumchenko E, Chatterjee A, kDa (PRAS40). J Cell Commun Signal, 13(2):163-177(2019) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: SGI-1776, Targeted therapy,Phosphoproteomics, Cell survival, Gastrointestinal cancer, PI3K/AKT/mTOR

Harsha Gowda
contact affiliation	Institute of Bioinformatics, 7th floor, Discoverer building, International Tech Park, Bangalore 560 066, India
contact email	harsha@ibioinformatics.org
lab head
Harsha Gowda
contact affiliation	QIMR Berghofer Medical Research Institute
contact email	harsha@ibioinformatics.org
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/2019/01/PXD007946

PRIDE project URI

• PRIDE
  1. PXD007946
     1. Label: PRIDE project
     2. Name: PIM1 kinase promotes gallbladder cancer cell proliferation via inhibition of proline-rich Akt substrate of 40 kDa (PRAS40)