DEPDC1 (DEP domain containing 1) functions as an oncogenic regulator promoting malignant progression across multiple cancer types through diverse signaling mechanisms. Primary Function: DEPDC1 acts as a transcriptional coregulator and protein-interaction hub that enhances cancer cell proliferation, survival, and metabolic reprogramming. Mechanism: DEPDC1 operates through multiple pathways depending on cancer context. In renal cell carcinoma, DEPDC1 promotes glycolysis via the AKT/mTOR/HIF1α pathway 1. In hepatocellular carcinoma, it activates JNK signaling to suppress apoptosis and enhance chemotherapy resistance 2. DEPDC1 interacts with protein partners including KIF20A (activating PI3K/AKT/mTOR pathway in liposarcoma) 3, FOXM1 (facilitating Wnt/β-catenin signaling in oral squamous cell carcinoma) 4, and S100A16 (promoting PI3K/Akt/mTOR pathway in nephroblastoma) 5. DEPDC1 expression is transcriptionally repressed by FOXO3a in nephroblastoma 6, and p53 inactivation upregulates DEPDC1 as a cofactor for SCD1-mediated fatty acid synthesis in breast cancer brain metastasis 7. Disease Relevance: High DEPDC1 expression correlates with poor prognosis and predicts metastasis across hepatocellular carcinoma 2, renal cell carcinoma 1, liposarcoma 3, and gastric cancer 8. Clinical Significance: DEPDC1 represents a potential therapeutic target, particularly for TKI-resistant renal cell carcinoma when combined with metabolic therapy 1.