MMP11 promotes the proliferation and progression of breast cancer through stabilizing Smad2 protein

Abstract

Breast cancer (BC) is one of the most common malignant tumours in women. The matrix metalloproteinase (MMP) enzyme family plays a complex role in the development of BC. There is increasing evidence that MMP11 plays a major role in BC; however, the underlying mechanisms are not clear. The present study confirmed by analysing clinical samples and TCGA data sets, that high expression of MMP11 in clinical samples of BC was strongly associated with a poor prognosis in BC patients. In addition, MTT and colony formation assays indicated that the proliferative capacity of BC was affected when MMP11 expression changed. Furthermore, pathway enrichment analysis was performed and it was revealed that the TGF-β signalling pathway was a potential downstream target of MMP11. In the TGF-β signalling pathway, MMP11 could significantly regulate the protein expression levels of Smad2 and Smad3 and inhibit the degradation of Smad2 through the ubiquitin proteasome pathway as determined by western blotting. In vivo, it was further verified that MMP11 knockdown could inhibit tumour proliferation and growth. Collectively, the present results demonstrated that MMP11 inhibited the degradation of Smad2 in the TGF-β signalling pathway, thereby promoting the development of BC. Thus, MMP11 expression was not only revealed to be an important indicator of BC prognosis but may also be an important therapeutic target for further prevention of BC growth and proliferation. The present study indicated that MMP11-targeted therapy may provide new solutions for BC treatment.