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TNK2 Tyrosine Kinase as a Novel Therapeutic Target in Triple Negative Breast Cancer

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Johns Hopkins University Baltimore United States

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Triple-negative breast cancers TNBCs represent only 10-15 of all breast cancers however, they are highly aggressive and have a higher rate of metastasis. In order to explore the role of tyrosine kinase signaling in TNBCs, we have performed global phosphotyrosine profiling for a panel of 25 TNBC cell lines. When we correlated protein phosphorylation levels with cellular oncogenic phenotypes, we observed a novel non-receptor tyrosine kinase, TNK2, to be hyperphosphorylated and activated in highly aggressive TNBC cells. Suppression of TNK2 by specific siRNAs significantly reduced the proliferation, colony formation, and invasiveability of TNBC cells. The objective of this proposal is to evaluate the therapeutic potential of TNK2 in the treatment of TNBCs. The Specific Aims of this project are Aim 1 DoTNK2 protein levels and activation correlate with clinical and pathological features of TNBC Aim 2 What is the value of TNK2 as a therapeutic target in vitro and in preclinical animal models Aim 3 How is TNK2 signaling altered during oncogenesis in TNBCs

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Technical Report,30 Sep 2015,29 Sep 2016



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Approved For Public Release;

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