Mbip, short for MAP3K12 binding inhibitory protein, is a component of the Ada2A containing complex (ATAC) and has been associated with multiple biological processes and diseases. It interacts with MUK/DLK/ZPK, a MAPKKK class protein kinase, and inhibits its activity to induce JNK/SAPK activation, suggesting its role in the regulation of the JNK pathway [4].

In cancer research, studies have shown its significant impact. In esophageal squamous cell carcinoma (ESCC), Mbip expression is higher in cancer tissue compared to normal tissue. High Mbip expression is linked to deeper invasion and worse prognosis. Overexpression promotes migration and invasion in vitro and in vivo, while knockdown has the opposite effect. It promotes epithelial-mesenchymal transition (EMT) via phosphorylation of JNK/p38 [1]. In non-small cell lung cancer (NSCLC), Mbip expression enhances cellular proliferation, migration, and invasion in vitro and metastasis in vivo. It mediates JNK pathway activation and induces matrix metalloproteinases (MMPs) expression, which are crucial for the invasive and metastatic phenotype [2]. Additionally, certain SNPs in the Mbip gene are associated with breast cancer risk. SNPs like rs3168891 in Mbip may alter its role in the inactivation of the mitogen-activated protein kinase (MAPK) pathway, potentially contributing to breast cancer susceptibility [3,5].

In conclusion, Mbip plays essential roles in cancer metastasis and disease susceptibility, especially in ESCC, NSCLC, and breast cancer, mainly through its influence on the JNK and MAPK pathways. The understanding of Mbip's function through various genetic models has provided insights into the molecular mechanisms underlying these diseases, potentially offering new directions for therapeutic strategies.