Mmp16, also known as membrane-type 3 matrix metalloproteinase (MT3-MMP), is a zinc-containing endopeptidase belonging to the membrane-type (MT) MMPs subgroup. MMPs are enzymes capable of degrading various extracellular matrix (ECM) proteins, and their actions on ECM contribute to multiple biological processes [2].

In the context of diseases, in hepatocellular carcinoma (HCC), MMP16 is a prognostic factor. High expression in patients predicts poor overall survival, and knockdown of MMP16 in HCC cells weakens their invasive potential by inhibiting the epithelial-mesenchymal transition (EMT) process [3].

In gastric cancer, high MMP16 expression is correlated with poor prognosis as it promotes cell proliferation and invasion, and silencing MMP16 decreases these capacities [5].

In melanoma, copy-number gain or overexpression of MMP16 is linked to poor clinical outcome, collagen bundle assembly around tumor cell nests, and lymphatic invasion. Silencing MMP16 in melanoma cells leads to cell-surface accumulation of its substrates and affects cell-cell adhesion, collagen alignment, and lymphatic invasion [4].

In non-syndromic cleft lip with or without palate (NSCL ± P), association analysis identified MMP16 susceptible single-nucleotide polymorphisms (SNPs), emphasizing its potential role in lip development [1].

In conclusion, MMP16 is an important enzyme involved in ECM degradation. Its dysregulation is associated with multiple cancers and a congenital disorder. Studies, including those using loss-of-function models in cancer cells, have revealed its oncogenic role in promoting tumor invasion, metastasis, and proliferation, as well as its potential role in lip development, highlighting its significance in understanding disease mechanisms and potential therapeutic targeting.