title: Gli1 enhances migration and invasion via up-regulation of MMP-11 and promotes metastasis in ERα negative breast cancer cell lines.
abstract: 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.
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors: Yeon-Jin
authors: YJ
authors: Kwon
authors: Douglas R
authors: DR
authors: Hurst
authors: Adam D
authors: AD
authors: Steg
authors: Kun
authors: K
authors: Yuan
authors: Kedar S
authors: KS
authors: Vaidya
authors: Danny R
authors: DR
authors: Welch
authors: Andra R
authors: AR
authors: Frost
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D047628:Estrogen Receptor alpha / Q000172:deficiency*; D005260:Female; D006801:Humans; D053507:Matrix Metalloproteinase 11 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000071676:Zinc Finger Protein GLI1
chemical_list: D047628:Estrogen Receptor alpha; C400551:GLI1 protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D053507:Matrix Metalloproteinase 11