The non-receptor tyrosine kinase TNK2/ACK1 is a novel therapeutic target in triple negative breast cancer

Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Dhanashree S. Kelkar, Mustafa A. Bharbuiya, Pamela L. Rojas, Vered Stearns, Edward Gabrielson, Pavani Malla, Saraswati Sukumar, Nupam P. Mahajan, Akhilesh Pandey

Research output: Contribution to journalArticle

Abstract

Breast cancer is the most prevalent cancer in women worldwide. About 15-20% of all breast cancers do not express estrogen receptor, progesterone receptor or HER2 receptor and hence are collectively classified as triple negative breast cancer (TNBC). These tumors are often relatively aggressive when compared to other types of breast cancer, and this issue is compounded by the lack of effective targeted therapy. In our previous phosphoproteomic profiling effort, we identified the non-receptor tyrosine kinase TNK2 as activated in a majority of aggressive TNBC cell lines. In the current study, we show that high expression of TNK2 in breast cancer cell lines correlates with high proliferation, invasion and colony forming ability. We demonstrate that knockdown of TNK2 expression can substantially suppress the invasiveness and proliferation advantage of TNBC cells in vitro and tumor formation in xenograft mouse models. Moreover, inhibition of TNK2 with small molecule inhibitor (R)-9bMS significantly compromised TNBC proliferation. Finally, we find that high levels of TNK2 expression in high-grade basal-like breast cancers correlates significantly with poorer patient outcome. Taken together, our study suggests that TNK2 is a novel potential therapeutic target for the treatment of TNBC.

Original languageEnglish (US)
Pages (from-to)2971-2983
Number of pages13
JournalOncotarget
Volume8
Issue number2
DOIs
StatePublished - Jan 1 2017

Keywords

  • Phosphorylation
  • TNK2
  • Triple negative breast cancer
  • Tyrosine kinase

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Wu, X., Zahari, M. S., Renuse, S., Kelkar, D. S., Bharbuiya, M. A., Rojas, P. L., Stearns, V., Gabrielson, E., Malla, P., Sukumar, S., Mahajan, N. P., & Pandey, A. (2017). The non-receptor tyrosine kinase TNK2/ACK1 is a novel therapeutic target in triple negative breast cancer. Oncotarget, 8(2), 2971-2983. https://doi.org/10.18632/oncotarget.13579