Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Autophagy. 2021 Apr;17(4):1059-1060. doi: 10.1080/15548627.2021.1907168. Epub 2021 Mar 28.
Macroautophagy/autophagy modulation is increasingly recognized as a potential strategy for cancer therapy. Using a recently developed mutant 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 and -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.
自噬/自噬调节作用正逐渐被认为是一种潜在的癌症治疗策略。我们利用最近开发的突变敲入小鼠模型，通过严格的遗传方法，评估了其自噬和非经典功能在 ERBB2 驱动的 BrCA 模型中的作用。我们发现，自噬阻断几乎完全消除了 ERBB2 驱动的模型中的乳腺肿瘤发生，其抑制效果强于我们之前使用 PyMT 和 -null 小鼠模型的研究。从机制上讲，自噬抑制会扰乱 ERBB2 的细胞内运输，并通过小细胞外囊泡触发其释放。我们的研究结果证明了自噬在 ERBB2 驱动的 BrCA 中促进肿瘤发生的新机制，并可能为当前的抗 ERBB2 治疗策略提供补充。
