Increased autophagy blocks HER2-mediated breast tumorigenesis

作者：Silvia Vega-Rubín-de-Celis, Zhongju Zou, Álvaro F. Fernández, Bo Ci, Min Kim, Guanghua Xiao, Yang Xie, Beth Levine · 发表于：Proceedings of the National Academy of Sciences · 年份：2018 · DOI：10.1073/pnas.1717800115 · 被引用次数：138 · 研究领域：Autophagy in Disease and Therapy、Cancer-related gene regulation、Ubiquitin and proteasome pathways

are protected from HER2-driven mammary tumorigenesis, and HER2 fails to inhibit autophagy in primary cells derived from these mice. Moreover, treatment of mice with HER2-positive human breast cancer xenografts with the Tat-Beclin 1 autophagy-inducing peptide inhibits tumor growth as effectively as a clinically used HER2 tyrosine kinase inhibitor (TKI). This inhibition of tumor growth is associated with a robust induction of autophagy, a disruption of HER2/Beclin 1 binding, and a transcriptional signature in the tumors distinct from that observed with HER2 TKI treatment. Taken together, these findings indicate that the HER2-mediated inhibition of Beclin 1 and autophagy likely contributes to HER2-mediated tumorigenesis and that strategies to block HER2/Beclin 1 binding and/or increase autophagy may represent a new therapeutic approach for HER2-positive breast cancers.