Abstract
HKDC1 (hexokinase domain containing 1) is recognized as an oncogene in various cancers, yet its role in colorectal cancer (CRC) remains unclear. This study aims to explore HKDC1 expression in CRC and its effects on tumor growth, migration, glycolysis, and EMT, as well as the underlying molecular mechanisms. Using TIMER2.0 and TCGA databases, we analyzed HKDC1 expression across multiple cancers and evaluated its prognostic value via Kaplan-Meier survival analysis. HKDC1 expression in CRC tissues was validated through western blotting, immunohistochemistry, and qRT-PCR, and its correlation with patient prognosis was assessed. Functional experiments involving HKDC1 knockdown and overexpression were performed to examine their impact on CRC cell proliferation, migration, apoptosis, and the cell cycle. Coimmunoprecipitation, immunofluorescence, and mass spectrometry identified HKDC1's interaction with RCOR1, demonstrating its regulation of the Wnt/β-catenin pathway to promote CRC progression. High HKDC1 expression in CRC tissues correlated with poor patient prognosis. Knockdown of HKDC1 significantly reduced cell proliferation and migration, induced G1 phase arrest, and promoted apoptosis, whereas HKDC1 overexpression had the opposite effects. Additionally, HKDC1 promoted EMT and glycolysis through the Wnt/β-catenin signaling pathway. In vivo, HKDC1 knockdown inhibited tumor growth, while overexpression accelerated tumor progression. This study is the first to demonstrate that HKDC1 enhances CRC proliferation, migration, glycolysis, and EMT by modulating RCOR1 and activating the Wnt/β-catenin pathway. These findings suggest that HKDC1 could serve as a potential therapeutic target and prognostic marker for CRC, offering new insights for personalized treatment strategies.