Profilin-1 is a negative regulator of mammary carcinoma aggressiveness
| Autor: | Alan Wells, V Panchapakesa, Partha Roy, Li Zou, Tuhin Das, Maria Jaramillo, Diana Whaley |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Pathology cell migration MDA-MB-231 Mice Profilins 0302 clinical medicine Cell Movement Carcinoma Small Cell Neoplasm Metastasis Cells Cultured Cytoskeleton 0303 health sciences biology Cell migration 3. Good health Up-Regulation Oncology Profilin 030220 oncology & carcinogenesis Female Protein Binding medicine.medical_specialty Carcinogenicity Tests ligand interactions Motility Down-Regulation Mice Nude Breast Neoplasms Focal adhesion 03 medical and health sciences Breast cancer breast cancer medicine Cell Adhesion Animals Humans profilin Cell adhesion 030304 developmental biology HMEC Matrigel Cancer Mammary Neoplasms Experimental medicine.disease Actins Disease Models Animal Gene Expression Regulation Cancer research biology.protein Translational Therapeutics Neoplasm Transplantation |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Expression of profilin-1 (Pfn1) is downregulated in breast cancer cells, the functional significance of which is yet to be understood. To address this question, in this study we evaluated how perturbing Pfn1 affects motility and invasion of breast cancer cells. We show that loss of Pfn1 expression leads to enhanced motility and matrigel invasiveness of MDA-MB-231 breast cancer cells. Interestingly, silencing Pfn1 expression is associated with downregulation of both cell–cell and cell–matrix adhesions with concomitant increase in motility and dramatic scattering of normal human mammary epithelial cells. Thus, these data for the first time suggest that loss of Pfn1 expression may have significance in breast cancer progression. Consistent with these findings, even a moderate overexpression of Pfn1 induces actin stress-fibres, upregulates focal adhesion, and dramatically inhibits motility and matrigel invasiveness of MDA-MB-231 cells. Using mutants of Pfn1 that are defective in binding to either actin or proline-rich ligands, we further show that overexpressed Pfn1 must have a functional actin-binding site to suppress cell motility. Finally, animal experiments reveal that overexpression of Pfn1 suppresses orthotopic tumorigenicity and micro-metastasis of MDA-MB-231 cells in nude mice. These data imply that perturbing Pfn1 could be a good molecular strategy to limit the aggressiveness of breast cancer cells. |
| Databáze: | OpenAIRE |
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