Mfge8, also known as Milk fat globule-epidermal growth factor 8, is a secreted protein with diverse functions. It binds to integrin families, such as αVβ3/αVβ5, α8β1, and integrin β3, and is involved in multiple signaling pathways including PI3K/AKT, ERK/AKT, and integrin-mediated signaling. It is important in processes like angiogenesis, fibrosis, efferocytosis, insulin signaling, neurogenesis, and cancer progression [1-6].

In esophageal squamous cell carcinoma, MFGE8 secreted by cancer-associated fibroblasts promotes angiogenesis, tumor proliferation, drug resistance, and metastasis by activating PI3K/AKT and ERK/AKT pathways, and targeting it can inhibit ESCC growth and metastasis [1].

In intestinal fibrosis, MFGE8 shows antifibrotic effects by inhibiting ECM production in normal control human intestinal myofibroblasts, acting through integrin-mediated signaling pathways [2].

In colorectal cancer, CRC-derived extracellular vesicles containing MFGE8 facilitate macrophage efferocytosis of cisplatin-induced apoptotic CRC cells, contributing to cisplatin resistance [3].

MFGE8 also inhibits insulin signaling through PTP1B, with serum levels correlating with insulin resistance in humans [4].

In rats with experimental subarachnoid hemorrhage, MFGE8 promotes adult hippocampal neurogenesis via the integrin β3/Akt signaling pathway [5].

In gastric cancer, MFGE8 promotes cancer progression by activating the IL-6/JAK/STAT3 signaling [6].

In conclusion, Mfge8 is involved in a wide range of biological functions, with its dysregulation contributing to various disease conditions such as cancer, fibrosis, and metabolic disorders. The study of Mfge8 using in vivo models helps to understand its role in these diseases, potentially providing new therapeutic targets for treatment [1-6].