PXD016777-1

PXD016777 is an original dataset announced via ProteomeXchange.

Title	Differential responses to kinase inhibition in FGFR2-addicted triple negative breast cancer cells: a quantitative phosphoproteomics study
Description	Fibroblast Growth Factor (FGF) dependent signalling is frequently activated in cancer by a variety of different mechanisms. However, the downstream signal transduction pathways involved are poorly characterised. Here a quantitative differential phosphoproteomics approach, SILAC, is applied to identify FGF-regulated phosphorylation events in two triple- negative breast tumour cell lines, MFM223 and SUM52PE, that exhibit amplified expression of FGF receptor 2 (FGFR2) and are dependent on continued FGFR2 signalling for cell viability. Comparative Gene Ontology proteome analysis revealed that SUM52PE cells were enriched in proteins associated with cell metabolism and MFM223 cells enriched in proteins associated with cell adhesion and migration. FGFR2 inhibition by SU5402 impacts a significant fraction of the observed phosphoproteome of these cells. This study expands the known landscape of FGF signalling and identifies many new targets for functional investigation. FGF signalling pathways are found to be flexible in architecture as both shared, and divergent, responses to inhibition of FGFR2 kinase activity in the canonical RAF/MAPK/ERK/RSK and PI3K/AKT/PDK/mTOR/S6K pathways are identified. Inhibition of phosphorylation-dependent negative-feedback pathways is observed, defining mechanisms of intrinsic resistance to FGFR2 inhibition. These findings have implications for the therapeutic application of FGFR inhibitors as they identify both common and divergent responses in cells harbouring the same genetic lesion and pathways of drug resistance.
HostingRepository	PRIDE
AnnounceDate	2020-05-20
AnnouncementXML	Submission_2020-05-19_22:53:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Debbie Cunningham
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-16 06:45:23	ID requested
⏵ 1	2020-05-19 22:53:39	announced

Cunningham DL, Sarhan AR, Creese AJ, Larkins KPB, Zhao H, Ferguson HR, Brookes K, Marusiak AA, Cooper HJ, Heath JK, Differential responses to kinase inhibition in FGFR2-addicted triple negative breast cancer cells: a quantitative phosphoproteomics study. Sci Rep, 10(1):7950(2020) [pubmed]

submitter keyword: FGF, SILAC, phosphorylation, SU5402, MAPK, mTOR

Debbie Cunningham
contact affiliation	SChool of Biosciences University of Birminghsam Birminghsm B15 2TT UK
contact email	d.cunningham@bham.ac.uk
lab head
Debbie Cunningham
contact affiliation	University of Birmingham
contact email	d.cunningham@bham.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016777
     1. Label: PRIDE project
     2. Name: Differential responses to kinase inhibition in FGFR2-addicted triple negative breast cancer cells: a quantitative phosphoproteomics study