title: EGFR overexpressing cells and tumors are dependent on autophagy for growth and survival.
abstract: OBJECTIVE
  The epidermal growth factor receptor (EGFR) is overexpressed, amplified or mutated in various human epithelial tumors, and is associated with tumor aggressiveness and therapy resistance. Autophagy activation provides a survival advantage for cells in the tumor microenvironment. In the current study, we assessed the potential of autophagy inhibition (using chloroquine (CQ)) in treatment of EGFR expressing tumors.
  
  
  METHODS
  Quantitative PCR, immunohistochemistry, clonogenic survival, proliferation assays and in vivo tumor growth were used to assess this potential.
  
  
  RESULTS
  We show that EGFR overexpressing xenografts are sensitive to CQ treatment and are sensitized to irradiation by autophagy inhibition. In HNSSC xenografts, a correlation between EGFR and expression of the autophagy marker LC3b is observed, suggesting a role for autophagy in EGFR expressing tumors. This observation was substantiated in cell lines, showing high EGFR expressing cells to be more sensitive to CQ addition as reflected by decreased proliferation and survival. Surprisingly high EGFR expressing cells display a lower autophagic flux.
  
  
  CONCLUSIONS
  The EGFR high expressing cells and tumors investigated in this study are highly dependent on autophagy for growth and survival. Inhibition of autophagy may therefore provide a novel treatment opportunity for EGFR overexpressing tumors.
authors.affiliation: Maastricht Radiation Oncology (MaastRO) Lab, GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Barry
authors.initials: B
authors.lastname: Jutten
authors.forename: Tom G
authors.initials: TG
authors.lastname: Keulers
authors.forename: Marco B E
authors.initials: MB
authors.lastname: Schaaf
authors.forename: Kim
authors.initials: K
authors.lastname: Savelkouls
authors.forename: Jan
authors.initials: J
authors.lastname: Theys
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: Marc A
authors.initials: MA
authors.lastname: Vooijs
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
authors.forename: Kasper M A
authors.initials: KM
authors.lastname: Rouschop
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002738:Chloroquine / Q000494:pharmacology; D066246:ErbB Receptors / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000502:physiology; D009369:Neoplasms / Q000473:pathology*
chemical_list: C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D002738:Chloroquine; D066246:ErbB Receptors
keywords: Autophagy; Chloroquine; EGFR; Irradiation