Proto-oncogene ACTR/AIB1 promotes cancer cell invasion by up-regulating specific matrix metalloproteinase expression.
Overexpression of ACTR/AIB1 is frequently found in different cancers with distant metastasis. To address its possible involvement in tumor metastasis, we performed invasion assays to examine the effect of ACTR alteration on the invasiveness of breast cancer cells (MDA-MB-231 or T-47D) and found that high levels of ACTR are required for their strong invasiveness. Molecular analysis indicates that ACTR functions as a coactivator of AP-1 to up-regulate the expression of matrix metalloproteinases such as MMP-7 and MMP-10 and reduce cell adhesion to specific extracellular matrix proteins. These novel findings provide a mechanistic link between ACTR and MMPs, and suggest that ACTR may also play an important role in cancer progression by facilitating tumor invasion.
Li
Li B
LB
Department of Biochemistry and Molecular Medicine, School of Medicine, University of California at Davis, Sacramento, CA 95817, USA.
Louie
Maggie C
MC
Chen
H-W
HW
Zou
June X
JX
D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D056921:Nuclear Receptor Coactivator 3; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D056921:Nuclear Receptor Coactivator 3; D020782:Matrix Metalloproteinases; D053506:Matrix Metalloproteinase 10; D020783:Matrix Metalloproteinase 7