miR-181 suppresses metastasis via MMP-14

Metastasis accounts for 90% of all cancer-related deaths. Much effort has been made to identify key molecules controlling metastasis. However, due to the complicated wiring of the cancer signaling networks, key players initiating cancer metastasis have not been defined. This situation has thwarted target-based drug discovery aimed at preventing cancer metastasis. Regardless of which molecules initiate tumor, cancer cells must be equipped with proteases for invasive behavior [1]. A key cell surface-anchored protease, membrane type 1-matrix metalloproteinase (MMP-14), plays a critical role in digesting basement membrane and extracellular matrices (ECMs) and in inducing cancer cell migration, thereby promoting cancer invasion and metastasis [2]. MMP-14 is highly expressed in most human cancers and correlates with breast cancer mortality [3]. However, the regulatory mechanism of upregulated MMP-14 expression in cancer is poorly understood. We, for the first time, demonstrated that MMP-14 is directly inhibited by miR-181a-5p through targeting the 3′ untranslated region (UTR) resulting in decreased cell migration, invasion, and angiogenesis [4]. This relation introduces the possibility of miR-181a-5p as a biomarker for prognosis, or as a target to prevent cancer metastasis.