In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4797-4797
Abstract:
About 10-15% of all breast cancers are basal-like breast cancers (BLBCs) that are highly aggressive and lack effective targeted therapeutic options as they lack ER, PR and Her-2. Reversible phosphorylation of proteins is one the most important post-translational modifications and is involved in almost all kinds of cellular processes. Tyrosine phosphorylation (pY) accounts for a minority of total phosphorylation, less than 0.1% by overall abundance. However, pY plays a disproportionately large role in diseases especially in cancer. More than half of the 90 tyrosine kinases identified in the human proteome have been implicated in cancer through gain-of-function mutations, gene amplification, overexpression, or as tumor suppressors and become attractive therapeutic targets. To assess activated tyrosine kinase signaling pathways in TNBCs, we collected a panel of 28 publicly available triple-negative breast cancer cell lines and systematically analyzed the invasiveness and anchorage independent growth of this panel of cell lines. We carried out global quantitative phosphotyrosine profiling using high resolution Fourier transform mass spectrometry. In all, we identified 2,133 tyrosine-phosphorylated peptides from more than 800 proteins. A number of tyrosine kinases were found to be differentially phosphorylated in different sets of breast cancer cells. Pathway analysis revealed that phosphorylation level of certain oncogenic kinases including EGFR, MET, FAK1 and SRC was elevated in a majority of basal-like breast cancer cells. Notably, multiple members of EPH receptor family, EPHA1, EPHA2, EPHA3, EPHB3 and EPHB4, were hyper-phosphorylated in multiple basal-like breast cancer cells. Supervised clustering analysis of phosphorylated proteins identified specific phospho-signatures that correlated with invasiveness and anti-anoikis colony formation ability. One of these hyper-phosphorylated proteins was DYRK2, a dual specificity tyrosine kinase. We observed that DYRK2 had an effect on colony formation and invasive ability on a subset of TNBC cell lines. Overall, our global phosphoproteomic study confirms high heterogeneity in the activation status of tyrosine kinases across triple negative breast cancer cells and suggests that some of them are attractive candidates as therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4797. doi:1538-7445.AM2012-4797
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-4797
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
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