STAT-mediated EGFR signaling in cancer.
The epidermal growth factor receptor (EGFR) and signal transducers and activators of transcription (STATs) are commonly expressed and activated in many malignancies. EGFR is an upstream activator of several pathways involved in tumor progression, and STATs activate selected genes involved in oncogenesis. There are several different mechanisms by which STAT proteins can mediate intracellular EGFR signaling, including direct activation of STATs by EGFR binding and indirect activation of STATs through Src-mediated EGFR signaling. EGFR likely activates STAT in a manner distinctive from other mechanisms of STAT activation; STAT5 can be phosphorylated in an EGF-dependent manner at unique sites, conferring novel functions. Cumulative evidence suggests that targeting EGFR signaling pathways at several levels may demonstrate synergistic therapeutic effects compared with targeting the upstream receptor alone. Thus, methods to inhibit EGFR in conjunction with oncogenic STATs may represent a novel therapeutic strategy for cancers characterized by upregulation of EGFR signaling.
Department of Otolaryngology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Kelly M
KM
Quesnelle
Amanda L
AL
Boehm
Jennifer R
JR
Grandis
D000818:Animals; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D050791:STAT Transcription Factors; D066246:ErbB Receptors