Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark.
Department of Oncology, Institute of Clinical Research, Odense University Hospital, 5000 Odense, Denmark.
Int J Mol Sci. 2022 Sep 2;23(17):10053. doi: 10.3390/ijms231710053.
Triple-negative breast cancer (TNBC) is a heterogeneous disease that accounts for 10-15% of all breast cancer cases. Within TNBC, the treatment of basal B is the most challenging due to its highly invasive potential, and thus treatments to suppress metastasis formation in this subgroup are urgently needed. However, the mechanisms underlying the metastatic ability of TNBC remain unclear. In the present study, we investigated the role of Aurora A and Bcl-xL in regulating basal B cell invasion. We found gene amplification and elevated protein expression in the basal B cells, which also showed increased invasiveness in vitro, compared to basal A cells. Chemical inhibition of Aurora A with alisertib and siRNA-mediated knockdown of decreased the number of invading cells compared to non-treated cells in basal B cell lines. The analysis of the correlation between and expression in TNBC and patient survival revealed significantly decreased relapse-free survival ( = 534, = 0.012) and distant metastasis-free survival ( = 424, = 0.017) in patients with primary tumors exhibiting a high combined expression of and . Together, our findings suggest that high levels of Aurora A and Bcl-xL promote metastasis, and inhibition of these proteins may suppress metastasis and improve patient survival in basal B TNBC.
三阴性乳腺癌（TNBC）是一种异质性疾病，占所有乳腺癌病例的 10-15%。在 TNBC 中，基底 B 型的治疗最为具有挑战性，因为它具有高度的侵袭性潜力，因此迫切需要针对该亚组抑制转移形成的治疗方法。然而，TNBC 转移能力的机制仍不清楚。在本研究中，我们研究了 Aurora A 和 Bcl-xL 在调节基底 B 细胞侵袭中的作用。我们发现基底 B 细胞中存在基因扩增和蛋白表达升高，与基底 A 细胞相比，其体外侵袭性也增加。用alisertib 抑制 Aurora A 的化学抑制和 siRNA 介导的敲低 与未处理的细胞相比，基底 B 细胞系中侵袭细胞的数量减少。对 TNBC 中 与 表达的相关性分析以及患者生存情况的分析表明，在原发性肿瘤中同时高表达 与 的患者，无复发生存率（=534，=0.012）和远处无转移生存率（=424，=0.017）显著降低。综上所述，我们的研究结果表明，高水平的 Aurora A 和 Bcl-xL 促进转移，抑制这些蛋白可能抑制转移并改善基底 B 型 TNBC 患者的生存。
