Autophagy inhibition perturbs ERBB2 trafficking and abolishes tumorigenesis in ERBB2-driven breast cancer.
Autophagy inhibition perturbs ERBB2 trafficking and abolishes tumorigenesis in ERBB2-driven breast cancer.
复制标题
自噬抑制扰乱 ERBB2 运输并消除 ERBB2 驱动的乳腺癌中的肿瘤发生。
DOI：
10.1080/15548627.2021.1907168
复制
发表时间：
2021
期刊：
影响因子：
13.3
通讯作者：
Guan,Jun-Lin
中科院分区：
文献类型：
--
作者：
Hao,Mingang;Yeo,SynKok;Guan,Jun-Lin
巨噬细胞自噬/自噬调节被认为是癌症治疗的一种潜在策略。使用最近开发的Rb1cc1突变敲击小鼠模型，我们采取了严格的遗传学方法来评估其自噬和非正则功能在ERBB2驱动的BRCA模型中的作用。我们发现，在ERBB2驱动的模型中，自噬取消实际上可以消除乳腺肿瘤的发生，表现出比我们之前使用PyMT和brca1基因缺失的小鼠模型更强的抑制作用。从机制上讲，自噬抑制扰乱了ERBB2在细胞内的运输，并通过细胞外小泡触发其释放。我们的结果表明，在ERBB2驱动的BRCA中，自噬促进肿瘤发生的新机制，并可以补充现有的抗ERBB2治疗策略。
Macroautophagy/autophagy modulation is increasingly recognized as a potential strategy for cancer therapy. Using a recently developedRb1cc1mutant knockin mice model, we have taken a rigorous genetic approach to assess the role of both its autophagy and non-canonical functions in an ERBB2-driven BrCA model. We found that autophagy abrogation virtually abolishes mammary tumorigenesis in the ERBB2-driven model, exhibiting stronger inhibitory effects than in our previous studies using PyMT andbrca1-null mouse models. Mechanistically, autophagy inhibition perturbs ERBB2 intracellular trafficking and triggers its release via small extracellular vesicles. Our results demonstrate a new mechanism for autophagy to promote tumorigenesis in ERBB2-driven BrCA and could supplement current strategies for anti-ERBB2 therapy.