βIII-tubulin regulates breast cancer metastases to the Brain

Deepak Kanojia, Ramin A. Morshed, Lingjiao Zhang, Jason M. Miska, Jian Qiao, Julius W. Kim, Peter Pytel, Irina V. Balyasnikova, Maciej S. Lesniak, Atique U. Ahmed

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Brain metastases occur in about 10% to 30% of breast cancer patients, which culminates in a poor prognosis. It is, therefore, critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brainpredominant markers and found an elevation of several neuronal markers (βIII-tubulin, Nestin, and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of bIII-tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2, and MDA-MB-468), which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells.

Original languageEnglish (US)
Pages (from-to)1152-1161
Number of pages10
JournalMolecular Cancer Therapeutics
Volume14
Issue number5
DOIs
StatePublished - May 1 2015

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kanojia, D., Morshed, R. A., Zhang, L., Miska, J. M., Qiao, J., Kim, J. W., Pytel, P., Balyasnikova, I. V., Lesniak, M. S., & Ahmed, A. U. (2015). βIII-tubulin regulates breast cancer metastases to the Brain. Molecular Cancer Therapeutics, 14(5), 1152-1161. https://doi.org/10.1158/1535-7163.MCT-14-0950