Autophagy inhibition perturbs ERBB2 trafficking and abolishes tumorigenesis in ERBB2-driven breast cancer

Autophagy. 2021 Apr;17(4):1059-1060. doi: 10.1080/15548627.2021.1907168. Epub 2021 Mar 28.

Abstract

Macroautophagy/autophagy modulation is increasingly recognized as a potential strategy for cancer therapy. Using a recently developed Rb1cc1 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 brca1-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.

Keywords: Autophagy; ERBB2-positive breast cancer; FIP200/RB1CC1; small extracellular vesicles.

Publication types

  • Research Support, N.I.H., Extramural
  • Comment

MeSH terms

  • Animals
  • Autophagy
  • Autophagy-Related Proteins
  • Breast Neoplasms* / genetics
  • Cell Transformation, Neoplastic
  • Extracellular Vesicles*
  • Humans
  • Mice
  • Receptor, ErbB-2 / genetics

Substances

  • Autophagy-Related Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2