TNK2 Tyrosine Kinase as a Novel Therapeutic Target in Triple Negative Breast Cancer
Abstract
Triple-negative breast cancers (TNBCs) represent only 10 percent-15 percent 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 invasive ability 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: Do TNK2 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?
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2018
- Accession Number
- AD1087022
Entities
People
- Akhilesh Pandey
Organizations
- Johns Hopkins University