Cell Division Cycle Associated 8 Is a Key Regulator of Tamoxifen Resistance in Breast Cancer

Purpose: Breast cancer (BC) is one of the most common malignancies globally, and millions of women worldwide are diagnosed with BC every year. Up to 70% of BC patients are estrogen receptor (ER)-positive. Numerous studies have shown that tamoxifen has a significant therapeutic effect on both primary and metastatic ER-positive BC patients. Although tamoxifen is currently one of the most successful therapeutic agents for BC, a significant proportion of patients will eventually become resistant to tamoxifen, leading to tumor recurrence and metastasis. Knowledge about the development of tamoxifen resistance in BC patients is still limited. Methods: We applied a loss-and-gain method to study the biological functional role of cell division cycle associated 8 (CDCA8) in tamoxifen resistance in BC cells. Results: We found that CDCA8 was significantly elevated in tamoxifen-resistant BC cells. Knockdown of CDCA8 expression significantly inhibited the proliferation of tamoxifen-resistant BC cells and reduced their resistance to tamoxifen. In contrast, overexpression of CDCA8 promoted the growth of tamoxifen-sensitive BC cells and induced their resistance to tamoxifen. Conclusion: In this study, we reported that CDCA8 is a key regulator of tamoxifen resistance in BC, suggesting that CDCA8 may serve as a potential therapeutic target for BC treatment.