title: Stress-induced endocytosis and degradation of epidermal growth factor receptor are two independent processes.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) is an important oncogenic protein in multiple types of cancer. Endocytosis and degradation of epidermal growth factor receptor (EGFR) are two key steps for down-regulation of cell surface level of EGFR and modulation of EGFR signaling. Stress conditions induce ligand-independent endocytosis and degradation of EGFR. However, it is not clear whether stress-induced endocytosis and degradation are consequential or two independent events.
  
  
  METHODS
  Endocytosis and degradation of EGFR in response to stress treatment and effects of the p38 inhibitor, the Caspase-3 inhibitor and the proteasomal inhibitor in cervical cancer HeLa cells were determined using immunoblotting and immunofluorescent staining assays.
  
  
  RESULTS
  Stress conditions, such as protein biosynthesis inhibition, UV light irradiation, and hyper-osmosis, induced both ligand-independent endocytosis and degradation of EGFR. Stress-induced endocytosis of EGFR relies on p38 kinase activity, while stress-induced degradation of EGFR is catalyzed by Caspase-3 activity. Inhibiting p38 kinase impairs only the endocytosis but not the degradation, while inhibiting Caspase-3 results in the opposite effect to inhibiting p38. Furthermore, proteasomal activity is required for stress-induced degradation of EGFR and cell death, but not for endocytosis.
  
  
  CONCLUSIONS
  The results indicate that stress-induced endocytosis and degradation are two independent events and suggest stress signaling may utilize a double-secure mechanism to down-regulate cell surface EGFR in cancer cells.
authors.affiliation: School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Peng
authors.affiliation: School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dai
authors.affiliation: School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
authors.affiliation: School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, China.
authors.forename: Genbao
authors.initials: G
authors.lastname: Shao
authors.affiliation: School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Sun
authors.affiliation: School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, China.
authors.forename: Wannian
authors.initials: W
authors.lastname: Yang
authors.affiliation: School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
keywords: Caspase; Degradation; EGFR; Endocytosis; Stress; p38