Neuronal Calcium Sensor 1 (NCS1) is a multifunctional Ca2+binding protein that affects a range of cellular processes beyond those related to neurons. Functional characterization of NCS1 in neuronal model systems suggests that NCS1 may influence oncogenic processes. To this end, the biological role of NCS1 was investigated by altering its endogenous expression in MCF7 and MB231 breast cancer (BCa) cells. Overexpression of NCS1 resulted in a more aggressive tumor phenotype demonstrated by a marked increase in invasion and motility, and a decrease in cellmatrix adhesion to collagen IV. Overexpression of NCS1 was also shown to increase the efficacy of paclitaxelinduced cell death in a manner that was independent of cellular proliferation. To determine the association between NCS1 and clinical outcome, NCS1 expression was measured in two independent BCa cohorts by the Automated Quantitative Analysis (AQUA) method of quantitative immunofluorescence. Elevated levels of NCS1 were significantly correlated with shorter survival rates. Furthermore, multivariate analysis demonstrated that NCS1 status was prognostic, independent of Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Factor 2 Receptor (HER2), and lymph node status. These findings indicate that NCS1 plays a role in the aggressive behavior of a subset of breast cancers and has therapeutic or biomarker potential. Implications: NCS1, a calcium binding protein, is associated with clinicopathological features of aggressiveness in breast cancer cells and worse outcome in two breast cancer patient cohorts.
- Received November 9, 2016.
- Revision received February 28, 2017.
- Accepted March 1, 2017.
- Copyright ©2017, American Association for Cancer Research.