Mbip, short for MAP3K12 binding inhibitory protein, is a component of the Ada2A containing complex (ATAC) and has been identified as a susceptibility gene in several cancers. It interacts with MAPK upstream kinase (MUK)/dual leucine zipper-bearing kinase/leucine-zipper protein kinase (MUK/DLK/ZPK) through its two tandemly orientated leucine-zipper-like motifs, and inhibits MUK/DLK/ZPK's activity to induce JNK/SAPK activation, thus regulating the MAPK pathway [4].

In esophageal squamous cell carcinoma (ESCC), Mbip expression is higher in cancer tissue than normal tissue. High Mbip expression is associated with deeper invasion and worse prognosis. Overexpression of Mbip promotes ESCC cell migration and invasion both in vitro and in vivo, while knockdown has the opposite effect. Mbip promotes epithelial-mesenchymal transition (EMT) via phosphorylation of JNK/p38 [1].

In non-small cell lung cancer (NSCLC), Mbip expression enhances cellular proliferation, migration, invasion in vitro and metastasis in vivo by mediating JNK pathway activation and inducing matrix metalloproteinases (MMPs) expression [2]. Also, certain SNPs in the Mbip gene are associated with an increased risk of breast cancer, and these SNPs may alter Mbip's role in the inactivation of the mitogen-activated protein kinase (MAPK) pathway [3,5].

In conclusion, Mbip plays a significant role in cancer metastasis and prognosis, especially in ESCC, NSCLC, and breast cancer, by regulating key signaling pathways. Studies on Mbip, including those using gene-knockout or knockdown models (implied by the functional changes upon knockdown), have enhanced our understanding of its function in cancer-related biological processes, providing potential biomarker and therapeutic target candidates for these cancers.