Institute of Reproductive Medicine, Medical School, Nantong University, Nantong, China.
Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
Cell Prolif. 2022 May;55(5):e13226. doi: 10.1111/cpr.13226. Epub 2022 Apr 10.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. However, the treatment regimens for TNBC are limited. Chromosome segregation 1-like (CSE1L), also called cellular apoptosis susceptibility protein (CAS), is highly expressed in breast cancer and plays a crucial role in the progression of various tumours. However, the involvement of CAS in TNBC remains elusive. In this study, we showed that the expression of CAS was higher in TNBC samples than in non-TNBC samples in the Gene Expression Omnibus database. Knockdown of CAS inhibited MDA-MB-231 cell growth, migration and invasion. Further RNA-seq analysis revealed that complement pathway activity was significantly elevated. Of note, complement component 3 (C3), the key molecule in the complement pathway, was significantly upregulated, and the expression of C3 was negatively correlated with that of CAS in breast cancer. Lower C3 expression was related to poor prognosis. Interestingly, the expression level of C3 was positively correlated with the infiltration of multiple immune cells. Taken together, our findings suggest that CAS participates in the development of TNBC through C3-mediated immune cell suppression and might constitute a potential therapeutic target for TNBC.
三阴性乳腺癌（TNBC）是乳腺癌中侵袭性最强的亚型。然而，TNBC 的治疗方案有限。染色体分离 1 样（CSE1L），也称为细胞凋亡易感性蛋白（CAS），在乳腺癌中高度表达，在各种肿瘤的进展中起着关键作用。然而，CAS 在 TNBC 中的参与仍然难以捉摸。在这项研究中，我们在基因表达综合数据库中显示，CAS 在 TNBC 样本中的表达高于非 TNBC 样本。CAS 的敲低抑制了 MDA-MB-231 细胞的生长、迁移和侵袭。进一步的 RNA-seq 分析显示补体途径活性显著升高。值得注意的是，补体成分 3（C3），补体途径的关键分子，显著上调，C3 的表达与乳腺癌中 CAS 的表达呈负相关。C3 表达较低与预后不良有关。有趣的是，C3 的表达水平与多种免疫细胞的浸润呈正相关。综上所述，我们的研究结果表明，CAS 通过 C3 介导的免疫细胞抑制参与了 TNBC 的发生，可能成为 TNBC 的潜在治疗靶点。
