Breast cancer antiestrogen resistance-3 expression regulates breast cancer cell migration through promotion of p130Cas membrane localization and membrane ruffling

Authors:
Schrecengost RS, Riggins RB, Thomas KS, Guerrero MS, Bouton AH
In:
Source: Cancer Res
Publication Date: (2007)
Issue: 67(13): 6174-82
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
MCF7
Species: human
Tissue Origin: breast
MCF7 tet
Species: human
Tissue Origin: breast
T-47D
Species: human
Tissue Origin: breast
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
Antiestrogens such as tamoxifen are widely used in the clinic to treat estrogen receptor-positive breast tumors. Resistance to tamoxifen can occur either de novo or develop over time in a large proportion of these tumors. Additionally, resistance is associated with enhanced motility and invasiveness in vitro. One molecule that has been implicated in tamoxifen resistance, breast cancer antiestrogen resistance-3 (BCAR3), has also been shown to regulate migration of fibroblasts. In this study, we investigated the role of BCAR3 in breast cancer cell migration and invasion. We found that BCAR3 was highly expressed in multiple breast cancer cell lines, where it associated with another protein, p130(Cas) (also known as breast cancer antiestrogen resistance-1; BCAR1), that plays a role in both tamoxifen resistance and cell motility. In cells with relatively low migratory potential, BCAR3 overexpression resulted in enhanced migration and colocalization with p130(Cas) at the cell membrane. Conversely, BCAR3 depletion from more aggressive breast cancer cell lines inhibited migration and invasion. This coincided with a relocalization of p130(Cas) away from the cell membrane and an attenuated response to epidermal growth factor stimulation that was characterized by a loss of membrane ruffles, decreased migration toward EGF, and disruption of p130(Cas)/Crk complexes. Based on these data, we propose that the spatial and temporal regulation of BCAR3/p130(Cas) interactions within the cell is important for controlling breast cancer cell motility.