Breast cancer antiestrogen resistance-3 expression regulates breast cancer cell migration through promotion of p130Cas membrane localization and membrane ruffling
| Autor: | Keena S. Thomas, Michael S. Guerrero, Randy S. Schrecengost, Amy H. Bouton, Rebecca B. Riggins |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
medicine.medical_specialty Membrane ruffling Cell Breast Neoplasms Biology Article Breast cancer Cell Movement Internal medicine Cell Line Tumor medicine Guanine Nucleotide Exchange Factors Humans Neoplasm Invasiveness skin and connective tissue diseases Adaptor Proteins Signal Transducing Epidermal Growth Factor Cell Membrane Cell migration Fibroblasts medicine.disease Antiestrogen Gene Expression Regulation Neoplastic Tamoxifen medicine.anatomical_structure Endocrinology Crk-Associated Substrate Protein Oncology Drug Resistance Neoplasm BCAR1 embryonic structures Cancer research BCAR3 RNA Interference hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Cancer research. 67(13) |
| ISSN: | 0008-5472 |
| Popis: | 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, p130Cas (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 p130Cas at the cell membrane. Conversely, BCAR3 depletion from more aggressive breast cancer cell lines inhibited migration and invasion. This coincided with a relocalization of p130Cas 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 p130Cas/Crk complexes. Based on these data, we propose that the spatial and temporal regulation of BCAR3/p130Cas interactions within the cell is important for controlling breast cancer cell motility. [Cancer Res 2007;67(13):6174–82] |
| Databáze: | OpenAIRE |
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