GCNT3, also known as mucin-type N-acetylglucosaminyltransferase 3, is a key regulator in mucin-type O-glycan synthesis. It is involved in multiple signaling pathways such as GSK3β/β-catenin, PI3K/AKT, and is associated with important biological processes in cancer development [1,2,3]. Genetic models, like gene knockout mouse models, are valuable for studying its function.

In hepatocellular carcinoma (HCC), GCNT3 overexpression promotes tumor formation and metastasis both in vitro and in vivo. It interacts with MUC13 to regulate its expression, activating the GSK3β/β-catenin signaling pathway [1]. Knockdown of MUC13 mitigates the activation of this pathway by GCNT3. In HCC specimens, high GCNT3 expression is correlated with poor patient survival [1]. Also, in HCC, GCNT3 promotes cell growth, migration, cell cycle progression, invasion, and epithelial-mesenchymal transition (EMT), while suppressing apoptosis, by activating the PI3K/AKT pathway [2].

In breast cancer, reducing GCNT3 expression significantly decreases cell proliferation, invasion, and migration, and increases apoptosis, with GCNT3 potentially activating the PI3K/AKT signaling pathway [3].

In lung adenocarcinoma, knockdown of GCNT3 decreases the proliferation, migration, and invasion capabilities of cells, and enhances the sensitivity to radiotherapy [4].

In castration-resistant prostate cancer cells, GCNT3 knockdown induces cell migration and EMT [5].

In conclusion, GCNT3 plays a crucial role in promoting cancer cell proliferation, migration, invasion, and EMT in various cancers including HCC, breast cancer, lung adenocarcinoma, and castration-resistant prostate cancer. Gene knockout or knockdown models have been instrumental in revealing these functions, highlighting GCNT3 as a potential target for cancer treatment in these disease areas.