ADAM12, also known as meltrin alpha, is a type I transmembrane multidomain protein. It has protease activity, cell binding, and cell signaling properties [3]. Functionally, it is involved in insulin-like growth factor (IGF) receptor signaling by cleaving IGF-binding proteins, and in epidermal growth factor receptor (EGFR) pathways via ectodomain shedding of membrane-tethered EGFR ligands [5]. These activities can regulate cell differentiation, proliferation, migration, and invasion [5].

In breast cancer, hypoxia-inducible factor-dependent ADAM12 expression mediates cancer invasion and metastasis. Inhibition of ADAM12 expression or activity decreased hypoxia-induced breast cancer cell migration and invasion in vitro, and impaired lung metastasis in mice [1]. In melanoma, pancreatic cancer, and prostate cancer mouse models, genetic depletion of slow-cycling PDGFRα+ADAM12+ mesenchymal cells restored antitumor immunity by restricting macrophage efferocytosis [2]. In clear cell renal cell carcinoma, knockdown of ADAM12 suppressed its oncogenic function, including cell proliferation, migration, and invasion, by inhibiting epithelial-mesenchymal transition (EMT) through the EGFR/ERK signaling pathway [4].

In conclusion, ADAM12 plays a significant role in multiple disease-related biological processes such as cancer invasion, metastasis, and immune regulation. Studies using gene knockout or conditional knockout mouse models have revealed its functions in breast, melanoma, pancreatic, prostate, and clear cell renal cell carcinomas, highlighting its potential as a therapeutic target in these disease areas.