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Mol Cancer Res. 2017 Jul;15(7):942-952. doi: 10.1158/1541-7786.MCR-16-0408. Epub 2017 Mar 8.

Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival.

Author information

1
Department of Experimental Pathology, Yale School of Medicine, New Haven, Connecticut.
2
Department of Pharmacology, Yale School of Medicine, New Haven, Connecticut.
3
Department of Experimental Pathology, Yale School of Medicine, New Haven, Connecticut. david.rimm@yale.edu.

Abstract

Neuronal Calcium Sensor 1 (NCS-1) is a multi-functional Ca2+-binding protein that affects a range of cellular processes beyond those related to neurons. Functional characterization of NCS-1 in neuronal model systems suggests that NCS-1 may influence oncogenic processes. To this end, the biological role of NCS-1 was investigated by altering its endogenous expression in MCF-7 and MB-231 breast cancer cells. Overexpression of NCS-1 resulted in a more aggressive tumor phenotype demonstrated by a marked increase in invasion and motility, and a decrease in cell-matrix adhesion to collagen IV. Overexpression of NCS-1 was also shown to increase the efficacy of paclitaxel-induced cell death in a manner that was independent of cellular proliferation. To determine the association between NCS-1 and clinical outcome, NCS-1 expression was measured in two independent breast cancer cohorts by the Automated Quantitative Analysis method of quantitative immunofluorescence. Elevated levels of NCS-1 were significantly correlated with shorter survival rates. Furthermore, multivariate analysis demonstrated that NCS-1 status was prognostic, independent of estrogen receptor, progesterone receptor, HER2, and lymph node status. These findings indicate that NCS-1 plays a role in the aggressive behavior of a subset of breast cancers and has therapeutic or biomarker potential.Implications: NCS-1, a calcium-binding protein, is associated with clinicopathologic features of aggressiveness in breast cancer cells and worse outcome in two breast cancer patient cohorts. Mol Cancer Res; 15(7); 942-52. ©2017 AACR.

PMID:
28275088
PMCID:
PMC5500411
DOI:
10.1158/1541-7786.MCR-16-0408
[Indexed for MEDLINE]
Free PMC Article

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