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

Abstract

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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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2016
Accession Number
AD1044325

Entities

People

  • Akhilesh Pandey

Organizations

  • Johns Hopkins University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Diseases And Disorders
  • Electronic Mail
  • Kinases
  • Mass Spectrometry
  • Neoplasms
  • Proteins
  • Small Molecules
  • Spectrometry
  • Statistical Analysis
  • Tyrosine

Fields of Study

  • Biology
  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology (Cancer Research).
  • Software Engineering.