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STAT‐mediated EGFR signaling in cancer
Author(s) -
Quesnelle Kelly M.,
Boehm Amanda L.,
Grandis Jennifer R.
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21475
Subject(s) - stat , stat5 , signal transduction , epidermal growth factor receptor , stat protein , cancer research , cyclin dependent kinase 8 , downregulation and upregulation , biology , transcription factor , carcinogenesis , activator (genetics) , microbiology and biotechnology , phosphorylation , receptor , stat3 , cancer , gene , notch signaling pathway , genetics
Abstract 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. J. Cell. Biochem. 102: 311–319, 2007. © 2007 Wiley‐Liss, Inc.