PXD007051

PXD007051 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics reveals network rewiring to a pro-adhesion state in Annexin-1-deficient mammary epithelial cells
Description	Background Annexin-1 (ANXA1) plays pivotal roles in regulating various physiological processes including inflammation, proliferation and apoptosis, and deregulations of ANXA1 functions have been associated with tumorigenesis and metastasis events in several cancers. Though ANXA1 levels correlate with breast cancer disease status and outcome, its distinct functional involvement in breast cancer initiation and progression remains unclear. We hypothesized ANXA1-responsive kinase signaling alteration and associated phosphorylation signaling underlie early events in breast cancer initiation events and hence profiled ANXA1-dependent phosphorylation changes in mammary gland epithelial cells. Methods Quantitative phosphoproteomics analysis of mammary gland epithelial cells derived from ANXA1-heterozygous and ANXA1-deficient mice was carried out using SILAC-based mass spectrometry. Kinase and signaling changes underlying ANXA1 perturbations were derived by upstream kinase prediction and integrated network analysis of altered proteins and phosphoproteins. Results We identified a total of 8,110 unique phosphorylation sites, of which 582 phosphorylation sites on 372 proteins showed ANXA1-responsive changes. A majority of these phosphorylation changes occurred on proteins associated with cytoskeletal reorganization spanning the focal adhesion, stress fibers, and also the microtubule network pressing on new roles for ANXA1 in regulating microtubule dynamics. Comparative analysis of regulated global proteome and phosphoproteome highlighted key differences in translational and post-translational effects of ANXA1, and stressed on a close-coordinated rewiring of the cell adhesion network. Kinase prediction analysis suggested activity modulation of CAMK2, PAK, ERK, and IKK kinases upon loss of ANXA1. Integrative analysis revealed regulation of WNT and also Hippo signaling pathways in ANXA1-deficient mammary epithelial cells, wherein there is a downregulation of transcriptional effects of TEAD suggestive of ANXA1-responsive transcriptional rewiring. Conclusions The phosphoproteome landscape uncovered several novel perspectives for ANXA1 in mammary gland biology and stressed on its involvement in key signaling pathways modulating cell adhesion and migration that could contribute to breast cancer initiation.
HostingRepository	PRIDE
AnnounceDate	2017-12-13
AnnouncementXML	Submission_2018-05-23_06:58:05.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sheena Wee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-14 06:30:46	ID requested
1	2017-12-13 05:23:40	announced
⏵ 2	2018-05-23 06:58:07	announced	Updated publication reference for PubMed record(s): 29233185.

Alli-Shaik A, Wee S, Lim LHK, Gunaratne J, Phosphoproteomics reveals network rewiring to a pro-adhesion state in annexin-1-deficient mammary epithelial cells. Breast Cancer Res, 19(1):132(2017) [pubmed]

curator keyword: Biological

submitter keyword: Annexin-1, breast cancer, proteomics, phosphoproteomics, network analysis, adhesion, mammary epithelial cells

Jayantha Gunaratne
contact affiliation	Translational Biomedical Proteomics, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673
contact email	jayanthag@imcb.a-star.edu.sg
lab head
Sheena Wee
contact affiliation	IMCB
contact email	swee@imcb.a-star.edu.sg
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007051
     1. Label: PRIDE project
     2. Name: Phosphoproteomics reveals network rewiring to a pro-adhesion state in Annexin-1-deficient mammary epithelial cells