1. NIP1/DUOXA1 expression in epithelial breast cancer cells: regulation of cell adhesion and actin dynamics.
- Author
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Ostrakhovitch EA and Li SS
- Subjects
- Blotting, Western, Breast Neoplasms genetics, Cell Adhesion physiology, Cell Line, Tumor, Cell Separation, Cyclin-Dependent Kinase Inhibitor p21 genetics, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Cytoskeleton metabolism, Dual Oxidases, Epithelial Cells metabolism, Female, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression, Humans, NADPH Oxidases, Nuclear Cap-Binding Protein Complex genetics, Reactive Oxygen Species metabolism, Reverse Transcriptase Polymerase Chain Reaction, Transfection, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Actins metabolism, Breast Neoplasms metabolism, Gene Expression Regulation, Neoplastic genetics, Nuclear Cap-Binding Protein Complex biosynthesis
- Abstract
DUOXA1/NIP1, originally identified as a Numb-interacting protein, was recently shown to function as a maturation factor for the dual oxidase 1(DUOX1). In this study, we identified DUOXA1/NIP1 expression in breast cancer cells, observed high expression of DUOXA1 in non-invasive MCF7 cells and low expression in highly metastatic cells with impaired p53 functions linking the expression of DUOXA1 with p53. An inhibition of cell proliferation associated with upregulation of p21(Cip1/WAF1) was observed in MDA-MB-231 cells following transfection of DUOXA1. The transient DUOXA1 overexpression also inhibited expression of cell-surface integrin alphaVbeta5 and CD9, which is associated with impaired spreading ability. However, there was no difference in expression of these proteins in DUOX1-depleted cells. The observed effects coincided with an increase in reactive oxygen species (ROS) generation. Our data also demonstrate that DUOXA1 transient overexpression affected the cell-cell adhesion by modulating the actin cytoskeleton, and sensitized cells to doxorubicin.
- Published
- 2010
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