UBE2M与雌激素受体形成一个积极的反循环,以推动乳腺癌的进展和药物耐药性
Xiongzhi Lin1,2, Dongsheng Sun1, Shuhan Yang1
1Taizhou Central Hospital (Taizhou University Hospital), School of Medicine, Taizhou University, Taizhou, Zhejiang, China.
Cell death & disease
|August 13, 2024
概括
一个关键的酶UBE2M通过与ERα形成反循环,驱动雌激素受体阳性乳腺癌的生长和对富勒韦斯特兰的抵抗. 准UBE2M为这种癌症类型提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- UBE2M (Ubiquitin-like修饰剂激活酶1) 是一种NEDD8结合酶,涉及各种癌症.
- 它在雌激素受体阳性 (ER +) 乳腺癌中的特定作用及其与预后的关联以前是未知的.
研究的目的:
- 调查UBE2M在ER+乳腺癌中的作用.
- 阐明UBE2M在这种情况下的功能背后的分子机制.
- 评估针对ER+乳腺癌中的UBE2M的治疗潜力.
主要方法:
- 在ER+与ER-乳腺癌组织中对UBE2M表达的比较分析.
- 对 UBE2M 表达式的预测值评估.
- 调查UBE2M和ERα之间的反循环,包括转录和无处不在的途径.
- 功能性研究涉及体外和体内UBE2M沉默,评估细胞生长,细胞循环,细胞亡和对富尔韦斯特兰特的反应.
主要成果:
- 在ER+乳腺癌组织中,UBE2M的表达显著更高,与预后较差相关.
- 一个积极的反循环存在,其中ERα增强了UBE2M转录 (通过HIF-1α),而UBE2M通过抑制其无处不在和降解来稳定ERα.
- 沉默UBE2M抑制乳腺癌细胞生长,诱导细胞循环停止和细胞亡,并增强对fulvestrant的敏感性.
结论:
- UBE2M-ERα反循环促进了ER+乳腺癌的进展和富尔韦斯坦抗药性.
- 在ER+乳腺癌中,UBE2M代表了内分泌治疗的有前途的治疗标.
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