三阴性乳腺癌（TNBC）是一种侵袭性疾病，目前尚无有效的治疗靶点和显着的生物标志物。精子相关抗原 5 (SPAG5) 是一种有丝分裂纺锤体相关蛋白，在多种人类癌症中具有致癌功能。在 TNBC 中，SPAG5 表达增加与肿瘤进展、化疗耐药、复发和不良临床结果相关。在这里，我们表明 TNBC 中 SPAG5 的高表达受到 YAP、突变体 p53 和 MYC 协调活性的调节。 YAP 或突变 p53 蛋白的耗尽会减少 SPAG5 表达以及 MYC 募集到 SPAG5 启动子上。 MYC 的靶向还降低了 TNBC 细胞的 SPAG5 表达以及随之而来的致瘤性。 MYC 靶向的这些作用与细胞毒性化疗具有协同作用，并以 SPAG5 表达依赖性方式显着降低 TNBC 致癌性。这些结果表明，突变型 p53-MYC-SPAG5 表达可被视为患者结果的真实预测因子，以及有效抗癌治疗的可靠生物标志物。© 2024。作者。

Triple negative breast cancer (TNBC) is an aggressive disease which currently has no effective therapeutic targets and prominent biomarkers. The Sperm Associated antigen 5 (SPAG5) is a mitotic spindle associated protein with oncogenic function in several human cancers. In TNBC, increased SPAG5 expression has been associated with tumor progression, chemoresistance, relapse, and poor clinical outcome. Here we show that high SPAG5 expression in TNBC is regulated by coordinated activity of YAP, mutant p53 and MYC. Depletion of YAP or mutant p53 proteins reduced SPAG5 expression and the recruitment of MYC onto SPAG5 promoter. Targeting of MYC also reduced SPAG5 expression and concomitantly tumorigenicity of TNBC cells. These effects of MYC targeting were synergized with cytotoxic chemotherapy and markedly reduced TNBC oncogenicity in SPAG5-expression dependent manner. These results suggest that mutant p53-MYC-SPAG5 expression can be considered as bona fide predictors of patient's outcome, and reliable biomarkers for effective anticancer therapies.© 2024. The Author(s).