Characterization of TIMP-1 upregulated in breast carcinoma cells expressing an epithelial-to-mesenchymal transtion inducer, Snail

다국어 초록 (Multilingual Abstract)

A zinc-finger transcription factor Snail is an inducer of the epithelial-to-mesenchymal transition which downregulates E-cadherin and upregulates matrix metalloproteinases(MMPs) facilitating tumor progression and metastasis. Tissue inhibitor of metalloproteinases-1(TIMP-1) inhibits matrix metalloproteinases(MMPs) facilitating tumor progression and metastasis but its upregulation is associated with malignancy of various carcinomas. Here we demonstrate that expression of Snail in breast carcinoma MCF-7 cells upregulates TIMP-1 in a form that poorly inhibits MMPs. However, the TIMP-1 retains pro-survival function. Notably, MMP inhibition of the TIMP-1 was restored by removal of the N-glycans of the TIMP-1. Thus, N-glycan modification may be a general mechanism for regulating the ability of TIMP-1 to inhibit MMPs. Therefore, loss of the MMP-inhibiting function of TIMP-1 combined with its pro-survival effects may promote cancer progression and metastasis and help to explain the its paradoxical upregulation in various carcinomas.