PDZ-containing 1 (PDZK1) functions as a tumor suppressor in various cancers, but its role in cholangiocarcinoma (CCA) remains unclear. This study investigated the involvement of PDZK1 in CCA progression, particularly under hypoxic conditions that mimic late-stage tumors. Using lentiviral-mediated overexpression in CCLP and RBE cells, we assessed cell proliferation, apoptosis, migration, and glycolysis through CCK8, flow cytometry, wound healing assays, and measurements of glucose consumption, ATP, and lactate production. Hypoxia enhanced glycolytic activity and malignant behaviors while reducing PDZK1 expression. Overexpression of PDZK1 reversed these hypoxia-induced effects, suppressing proliferation, migration, and glycolysis, and promoting apoptosis. Mechanistically, PDZK1 overexpression downregulated hexokinase 2 (HK2) expression and activity, accompanied by reduced Akt phosphorylation. Activation of pAkt by perifosine partially abrogated the inhibitory effects of PDZK1 on glycolysis. These findings demonstrate that PDZK1 attenuates CCA progression under hypoxia by suppressing pAkt-mediated glycolysis, highlighting its potential as a therapeutic target for advanced CCA.

Yuangan Chen, Zhi Li. PDZK1 in Cholangiocarcinoma: Suppression of pAkt-Induced Glycolysis and Tumor Progression under Hypoxia. Frontiers in Medical Science Research (2026), Vol. 8, Issue 2: 59-68. https://doi.org/10.25236/FMSR.2026.080208.

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