Doxorubicin promotes breast cancer cell migration and invasion via DCAF13
Zhaoran Sun, Dongmei Zhou, Jinkui Yang, Daoyong Zhang
Abstract
DDB1 and CUL4 associated factor 13 (DCAF13) is a substrate receptor in the CUL4-DDB1 E3 ligase, and its expression is associated with the prognosis of certain cancers. In the present study, we report evidence that DCAF13 is aberrantly overexpressed in human breast cancer and its expression is positively associated with cancer progression. Further analysis showed that the DCAF13 expression level is significantly higher in triple-negative breast cancer compared to non-triple-negative breast cancer, indicating a positive correlation between its expression and the aggressiveness of breast cancer. Subsequent studies revealed that DCAF13 regulates cancer cell migration, invasion and epithelial-mesenchymal transition in human breast cancer, whereas it has no significant impact on breast cancer cell proliferation, cell cycle progressionor apoptosis. Taken together, our results demonstrate that DCAF13 promotes the epithelial-mesenchymal transition in human breast cancer cells, indicating an involvement in breast cancer metastasis. Furthermore, we report that doxorubicin, a widely used chemotherapy drug, increases DCAF13 expression in breast cancer cells, leading to enhanced cancer cell migration and invasion. These results suggest that doxorubicin chemotherapy may increase the risk of metastasis of drug-resistant breast cancer cells, and future therapeutics targeting DCAF13 may help reduce the risk, especially for patients undergoing chemotherapy.