Protector turns predator: Autophagic death via selective degradation of KRAS

Autophagy. 2013 Sep;9(9):1438-9. doi: 10.4161/auto.25837.

Abstract

Therapy-induced autophagy is recognized as a critical determinant of treatment outcome in cancer patients, primarily as a factor underlying drug resistance. However, recent investigations point toward a context-dependent, death-inducing role for autophagy, the mechanism of which remains largely unknown. Our recent study provides evidence that autophagy can directly mediate cell killing in multiple tumor cell types by facilitating degradation of KRAS/K-Ras, a key survival protein. These findings have broad implications for strategies employing autophagy modulation to target tumor cells.

Keywords: EGFR; KRAS; PRKC; autophagy; tamoxifen; tumor cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Autophagy* / drug effects
  • Cytoprotection* / drug effects
  • MAP Kinase Signaling System / drug effects
  • Protein Kinase C / metabolism
  • Proteolysis* / drug effects
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology

Substances

  • Tamoxifen
  • afimoxifene
  • Protein Kinase C
  • Proto-Oncogene Proteins p21(ras)