HDGF Knockout Suppresses Colorectal Cancer Progression and Drug Resistance by Modulating the DNA Damage Response
2025
Riya Su | Qin Wang | Qun Hu | Wendurige | Kexin Li | Changshan Wang | Liang Tao
Colorectal cancer (CRC) is a highly heterogeneous gastrointestinal malignancy. Despite significant advances in molecular targeted therapies for CRC in recent years, the increase in the overall survival rates for CRC patients remains limited. Therefore, there is an urgent need to explore novel drug targets. Herein, we show that heparin binding growth factor (HDGF) is highly expressed in CRC, and that its overexpression is associated with a poor disease-free interval. Additionally, we reveal that HDGF knockout reduces proliferation, migration, and invasion, while enhancing apoptosis in CRC cells, thereby validating HDGF as a potential therapeutic target for CRC. Mechanistically, we found that HDGF modulates DNA damage response and, by recruiting C-terminal binding protein-interacting protein (CtIP), it facilitates homologous recombination repair to influence CRC drug sensitivity. Furthermore, we propose that HDGF may serve as a recognition protein for H3K36me3, participating in the repair of damaged transcriptionally active genes, thus maintaining genomic stability in CRC.
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