SPZ1 is critical for chemoresistance and aggressiveness in drug-resistant breast cancer cells.

It is believed that chemotherapeutic agents can enhance the malignancy of treated cancer cells in clinical situations, which is a major problem for chemotherapy. However, the underlying molecular mechanisms are still not fully understood. Here, we demonstrated that chemotherapy up-regulates the levels of spermatogenic bHLH transcription factor zip 1 (SPZ1), and knockdown of SPZ1 in drug resistant breast cancers showed that SPZ1 is critical for regulating the chemoresistance, migration, invasion and epithelial-mesenchymal transition (EMT) in a Twist1-dependent manner. Moreover, suppressing SPZ1-Twist1 axis decreased the growth of tumor xenografts. Notably, we found a positive correlation between SPZ1 and Twist1 in breast cancer samples from patients with anthracycline or taxane-based chemotherapy. Thus, our results revealed a novel role of SPZ1 as an inducer of chemoresistance and aggressiveness under chemotherapy, and this suggests that therapeutic targeting of SPZ1 may not only enhance the sensitivity of breast cancer to chemotherapy, but also suppress breast cancer invasion and metastases.