CBX7通过Twist1/EphA2途径调控基底样乳腺癌的转移。
CBX7 regulates metastasis of basal-like breast cancer through Twist1/EphA2 pathway.
作者信息
Dai Tao, Liu Yiqi, Cao Renxian, Cao Jingying
机构信息
Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha 410013 Hunan Province, PR China.
The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China.
出版信息
Transl Oncol. 2022 Oct;24:101468. doi: 10.1016/j.tranon.2022.101468. Epub 2022 Jul 14.
BACKGROUND
Basal-like breast cancer (BLBC) is an important subtype of breast cancer. Twist1 is a key transcription factor in BLBC metastasis, which serves a key role in tumorigenesis. The potential mechanism of Twist1 in BLBC remains to be elucidated. Here, we explored the role and molecular mechanism of Twist1 in BLBC.
METHODS
The levels of CBX7, Twist1 and EphA2 in BLBC tissues and cells were determined by Western blot. ChIP and dual-luciferase reporter assays confirmed the interaction between CBX7, Twist1 and EphA2 promoter. The cellular functions were analyzed by CCK-8, colony formation, wound healing and Transwell assays. Expression of EMT related proteins was analyzed by Western blot. IHC measured the expression of CBX7, Twist1 and EphA2 in tumor tissues.
RESULTS
CBX7 was down-regulated in BLBC tissues and cells, whereas Twist1 and EphA2 were up-regulated. Twist1 silencing inhibited the cell migration, invasion and cancer metastasis of BLBC through targeting EphA2 and regulating EphA2 expression. Additionally, CBX7 blocked the binding of Twist1 to EphA2 promoter and inhibited EphA2 expression and suppressed BLBC growth and metastasis via Twist1/EphA2 axis.
CONCLUSION
CBX7 suppresses BLBC growth and metastasis through Twist1/EphA2 pathway. Our study may provide evidence and new therapeutic targets for the comprehensive treatment of BLBC.
背景
基底样乳腺癌（BLBC）是乳腺癌的一种重要亚型。Twist1是BLBC转移中的关键转录因子，在肿瘤发生中起关键作用。Twist1在BLBC中的潜在机制仍有待阐明。在此，我们探讨了Twist1在BLBC中的作用及分子机制。
方法
通过蛋白质免疫印迹法检测BLBC组织和细胞中CBX7、Twist1和EphA2的水平。染色质免疫沉淀（ChIP）和双荧光素酶报告基因检测证实了CBX7、Twist1与EphA2启动子之间的相互作用。通过细胞计数试剂盒-8（CCK-8）、集落形成、伤口愈合和Transwell检测分析细胞功能。通过蛋白质免疫印迹法分析上皮-间质转化（EMT）相关蛋白的表达。免疫组化法检测肿瘤组织中CBX7、Twist1和EphA2的表达。
结果
CBX7在BLBC组织和细胞中表达下调，而Twist1和EphA2表达上调。Twist1沉默通过靶向EphA2并调节EphA2表达来抑制BLBC的细胞迁移、侵袭和癌症转移。此外，CBX7阻断Twist1与EphA2启动子的结合，抑制EphA2表达，并通过Twist1/EphA2轴抑制BLBC的生长和转移。
结论
CBX7通过Twist1/EphA2途径抑制BLBC的生长和转移。我们的研究可能为BLBC的综合治疗提供证据和新的治疗靶点。
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