STAT signaling in head and neck cancer.
The upper aerodigestive tract is predisposed to the formation of multiple primary tumors due to field cancerization. TGF-alpha/EGFR autocrine signaling appears to play an important role in squamous cell carcinoma of the head and neck (SCCHN) and upregulation of TGF-alpha and EGFR is an early event in SCCHN carcinogenesis. STAT proteins, including Stat3, are activated by TGF-alpha and EGFR and strategies that downmodulate TGF-alpha or EGFR inhibit SCCHN cell proliferation and abrogate Stat3 activation. Targeting Stat3 leads to SCCHN growth inhibition, increases apoptosis and a downmodulation of Bcl-xL expression in head and neck tumors. These studies support the role of Stat3 as an oncogene, which is activated early in SCCHN carcinogenesis, and efforts to understand EGFR-mediated Stat3 signaling could facilitate novel strategies that will interfere with this growth promoting pathway. Oncogene (2000).
Song
J I
JI
Department of Otolaryngology, University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, PA 15213, USA.
Grandis
J R
JR
D017209:Apoptosis / Q000235:genetics; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016372:RNA, Antisense / Q000235:genetics; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000502:physiology
D004268:DNA-Binding Proteins; D016372:RNA, Antisense; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors