title: Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival.
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.
authors.affiliation: Department of Experimental Pathology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Moore
authors.affiliation: Department of Experimental Pathology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Allison
authors.initials: A
authors.lastname: England
authors.affiliation: Department of Pharmacology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Ehrlich
authors.affiliation: Department of Experimental Pathology, Yale School of Medicine, New Haven, Connecticut. david.rimm@yale.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics*; D051580:Neuronal Calcium-Sensor Proteins / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; C101464:frequenin calcium sensor proteins; C508053:ERBB2 protein, human