Survival of cancer cells is maintained by EGFR independent of its kinase activity.
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).
Weihua
Zhang
Z
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Tsan
Rachel
R
Huang
Wei-Chien
WC
Wu
Qiuyu
Q
Chiu
Chao-Hua
CH
Fidler
Isaiah J
IJ
Hung
Mien-Chie
MC
D001343:Autophagy; D016923:Cell Death; D002455:Cell Division; D002470:Cell Survival; D066246:ErbB Receptors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1 / Q000502:physiology*
D034741:RNA, Small Interfering; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D005947:Glucose