Matrix Metalloprotease-1a Promotes Tumorigenesis and Metastasis

摘要: Matrix metalloprotease-1 (MMP1), a collagenase and activator of the G protein-coupled protease activated receptor-1 (PAR1), is an emerging new target implicated in oncogenesis metastasis diverse cancers. However, functional mouse homologue MMP1 cancer models has not yet been clearly defined. We report here that Mmp1a promotes invasion metastatic progression lung melanoma. LLC1 (Lewis carcinoma) primary melanoma cells harboring active BRAF express high levels endogenous Mmp1a, which required for through collagen. Silencing either or PAR1 suppressed invasive stellate growth three-dimensional matrices. Conversely, ectopic expression conferred phenotype epithelial do Mmp1a. Consistent with acting as agonist autocrine loop, inhibition silencing resulted loss Mmp1a-driven phenotype. Knockdown on tumor significantly decreased tumorigenesis, invasion, xenograft models. Together, these data demonstrate cell-derived acts robust by conferring protumorigenic behavior to cells.