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Abstract：
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.
摘要：
认为化学治疗剂可以在临床情况下增强治疗的癌细胞的恶性程度。这是化疗的主要问题。然而,潜在的分子机制仍未完全了解。这里,我们证明化疗上调生精bHLH转录因子zip1（SPZ1）的水平，和SPZ1在耐药乳腺癌中的敲除表明，SPZ1对于调节化学耐药性至关重要，迁移,以Twist1依赖性方式进行侵袭和上皮-间质转化（EMT）。此外，抑制SPZ1-Twist1轴降低了肿瘤异种移植物的生长。值得注意的是,在接受蒽环类或紫杉烷类化疗患者的乳腺癌样本中,我们发现SPZ1和Twist1呈正相关.因此，我们的结果揭示了SPZ1作为化疗耐药和侵袭性诱导剂的新作用，这表明SPZ1的治疗靶向可能不仅增强乳腺癌对化疗的敏感性，而且还能抑制乳腺癌的侵袭和转移。
