PXD047577

PXD047577 is an original dataset announced via ProteomeXchange.

Title	Gas6/Axl signaling activates Akt in liver cancer cells
Description	We investigated which signaling pathways downstream of Gas6/Axl promote the invasive phenotype of liver cancer cells. Thus, we performed phospho-proteomic analysis of MR hepatocytes and those expressing Axl (MR-Axl) in the presence and absence of Gas6. Protein-clustering based on the pattern of phosphorylation across the conditions and samples revealed four clusters: phospho-sites that are upregulated dependent on Axl expression (cluster 1) or Gas6 expression (cluster 2) and phospho-sites that are downregulated dependent on Axl expression (cluster 3) or Gas6 expression (cluster 4). Functional enrichment analysis showed enrichment of protein sets associated with cellular polarity and motility depending on changes in Axl expression and Gas6 activation. Furthermore, we analyzed phospho-proteomic data to estimate the activity of kinases based on kinase-substrate interactions using PhosR. Kinase perturbation analysis indicated mammalian target of rapamycin (mTOR) as the one with the highest upregulated activity in Gas6-stimulated MR-Axl cells compared to Gas6-stimulated MR cells. Accordingly, we analyzed substrates of mTOR and found that phosphorylation of Akt1 (Ser473) was upregulated in cluster 1 and highly increased in Gas6-stimulated MR-Axl, suggesting that Akt is regulated by Axl.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:41:49.121.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	WeiQiang Chen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-06 08:26:50	ID requested
1	2024-05-22 23:56:19	announced
⏵ 2	2024-10-22 06:41:50	announced	2024-10-22: Updated project metadata.

10.3390/ijms25084202;

Breitenecker K, Heiden D, Demmer T, Weber G, Primorac AM, Hedrich V, Ortmayr G, Gruenberger T, Starlinger P, Herndler-Brandstetter D, Barozzi I, Mikulits W, Tumor-Extrinsic Axl Expression Shapes an Inflammatory Microenvironment Independent of Tumor Cell Promoting Axl Signaling in Hepatocellular Carcinoma. Int J Mol Sci, 25(8):(2024) [pubmed]

submitter keyword: cell invasion,Axl, hepatocellular carcinoma., Gas6

Wolfgang Mikulits
contact affiliation	Center for Cancer Research,Medical University of Vienna,Borschke-Gasse 8a,1090 Vienna
contact email	wolfgang.mikulits@meduniwien.ac.at
lab head
WeiQiang Chen
contact affiliation	Mass Spectrometry Facility, Max Perutz Laboratories Support GmbH
contact email	chenweiqiang@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047577
     1. Label: PRIDE project
     2. Name: Gas6/Axl signaling activates Akt in liver cancer cells