GALNT7 promotes hepatocellular carcinoma progression by activating the PI3K/AKT signaling pathway via O-glycosylation of MUC13.

Hepatocellular carcinoma (HCC) represents a significant global health challenge due to its aggressive malignancy. Abnormal glycosylation is a frequent phenomenon in tumor cells and manifests as alterations in key cancer biomarkers. This phenomenon is driven primarily by changes in the expressions of glycosyltransferases. Our study focuses on GALNT7, a member of the GALNT glycosyltransferase family, which catalyzes the initiation of O-linked glycan synthesis by transferring N-acetylgalactosamine (GalNAc) to serine or threonine residues on target proteins. We observe that GALNT7 expression is notably increased in HCC tissues and is correlated with increased tumor cell invasion, migration, and proliferation, alongside with reduced apoptosis, both in vivo and in vitro. Further molecular analyses indicate that GALNT7 specifically modifies the O-glycosylation pattern of MUC13, thereby influencing the activation of the PI3K/AKT signaling pathway. Additionally, elevated GALNT7 level enhances resistance to lenvatinib-based chemotherapy regimens. Thus, GALNT7 is a critical regulator of oncogenic processes in HCC. Targeting the GALNT7-MUC13-PI3K/AKT axis represents a novel therapeutic strategy for combating HCC.