Survival of cancer cells is maintained by EGFR independent of its kinase activity

Cancer Cell. 2008 May;13(5):385-93. doi: 10.1016/j.ccr.2008.03.015.

Abstract

Expression of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase associated with cell proliferation and survival, is overactive in many tumors of epithelial origin. Blockade of the kinase activity of EGFR has been used for cancer therapy; however, by itself, it does not seem to reach maximum therapeutic efficacy. We report here that in human cancer cells, the function of kinase-independent EGFR is to prevent autophagic cell death by maintaining intracellular glucose level through interaction and stabilization of the sodium/glucose cotransporter 1 (SGLT1).

Publication types

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

MeSH terms

  • Autophagy
  • Cell Death
  • Cell Division
  • Cell Survival
  • ErbB Receptors / deficiency
  • ErbB Receptors / genetics
  • ErbB Receptors / physiology*
  • Glucose / metabolism
  • Homeostasis
  • Humans
  • Kinetics
  • Neoplasm Metastasis
  • Neoplasms / pathology*
  • RNA, Small Interfering / genetics
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Sodium-Glucose Transporter 1 / physiology*

Substances

  • RNA, Small Interfering
  • SLC5A1 protein, human
  • Sodium-Glucose Transporter 1
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • Glucose