Gli1 enhances migration and invasion via up-regulation of MMP-11 and promotes metastasis in ERα negative breast cancer cell lines
| Autor: | Kedar S. Vaidya, Adam D. Steg, Yeon-Jin Kwon, Kun Yuan, Douglas R. Hurst, Danny R. Welch, Andra R. Frost |
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| Jazyk: | angličtina |
| Předmět: |
Cancer Research
Gli1 Estrogen receptor Breast Neoplasms Zinc Finger Protein GLI1 Metastasis 03 medical and health sciences Breast cancer 0302 clinical medicine Invasion Downregulation and upregulation Cell Movement Matrix Metalloproteinase 11 RNA interference GLI1 Tumor Cells Cultured medicine Humans Gene silencing Neoplasm Invasiveness Neoplasm Metastasis skin and connective tissue diseases Migration 030304 developmental biology 0303 health sciences biology Oncogene integumentary system Estrogen Receptor alpha Gli-mediated transcription General Medicine medicine.disease Up-Regulation 3. Good health Oncology 030220 oncology & carcinogenesis Cancer research biology.protein MMP-11 Female Research Paper Transcription Factors |
| Zdroj: | Clinical & Experimental Metastasis |
| ISSN: | 0262-0898 |
| DOI: | 10.1007/s10585-011-9382-z |
| Popis: | Gli1 is an established oncogene and its expression in Estrogen Receptor (ER) α negative and triple negative breast cancers is predictive of a poor prognosis; however, the biological functions regulated by Gli1 in breast cancer have not been extensively evaluated. Herein, Gli1 was over-expressed or down-regulated (by RNA interference and by expression of the repressor form of Gli3) in the ERα negative, human breast cancer cell lines MDA-MB-231 and SUM1315. Reduced expression of Gli1 in these two cell lines resulted in a decrease in migration and invasion. Gli1 over-expression increased the migration and invasion of MDA-MB-231 cells with a corresponding increase in expression of MMP-11. Silencing MMP-11 in MDA-MB-231 cells that over-expressed Gli1 abrogated the Gli1-induced enhancement of migration and invasion. Sustained suppression of Gli1 expression decreased growth of MDA-MB-231 in vitro by increasing apoptosis and decreasing proliferation. In addition, silencing of Gli1 reduced the numbers and sizes of pulmonary metastases of MDA-MB-231 in an in vivo experimental metastasis assay. In summary, Gli1 promotes the growth, survival, migration, invasion and metastasis of ERα negative breast cancer. Additionally, MMP-11 is up-regulated by Gli1 and mediates the migration and invasion induced by Gli1 in MDA-MB-231. Electronic supplementary material The online version of this article (doi:10.1007/s10585-011-9382-z) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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