Data from βIII-Tubulin Regulates Breast Cancer Metastases to the Brain

Abstract

<div>Abstract<p>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 brain-predominant 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, <i>in silico</i> analysis revealed overexpression of βIII-tubulin (<i>TUBB3</i>) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. <i>TUBB3</i> 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 <i>TUBB3</i> also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc <i>in vitro</i>. Furthermore, <i>TUBB3</i> knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability <i>in vivo</i>, and significantly improved survival in a brain metastasis model. These results implicate a critical role of <i>TUBB3</i> in conferring brain metastatic potential to breast cancer cells. <i>Mol Cancer Ther; 14(5); 1152–61. ©2015 AACR</i>.</p></div>