DCAF1 promotes the growth and metastasis of pancreatic cancer cells by activating the PTEN/PI3K/Akt signaling pathway.

Pancreatic cancer is a common malignant tumor of the digestive tract characterized by high mortality, primarily due to its aggressive proliferation and metastasis. DDB1-CUL4-associated factor 1 (DCAF1) has recently been identified as a cancer ‒ promoting gene in hepatocellular carcinoma and melanoma. However, its role and mechanism of action in pancreatic cancer remain largely unexplored. Analysis of the GEPIA database and experimental validation revealed that DCAF1 is significantly overexpressed in pancreatic cancer tissues and cell lines. Functional assays demonstrated that DCAF1 knockdown inhibited the proliferation, invasion, and migration of pancreatic cancer cells. Moreover, DCAF1 suppression impeded EMT, as evidenced by decreased expression of mesenchymal markers N-cadherin and α-SMA and increased expression of the epithelial marker E-cadherin. Knockdown of DCAF1 can inhibit Phosphatase and Tensin Homolog (PTEN) ubiquitination, leading to inactivation of the PI3K/Akt signaling pathway. In addition, the use of IGF-1 in the replenishment experiment can reverse the effect of knockdown of DCAF1, suggesting that DCAF1 may promote pancreatic cancer metastasis by activating this pathway. These findings suggest that DCAF1 functions as an oncogene in pancreatic cancer, promoting cell proliferation, migration, invasion, and EMT through activation of the PTEN/PI3K/Akt signaling pathway.