Constitutive activation of Stat3 correlates with increased expression of the c-Met/HGF receptor in oral squamous cell carcinoma.
Stat3 belongs to a family of signal transducers and activators of transcription. Constitutive activation of Stat3 has been observed in many human malignancies. In addition, mutated Stat3 has been shown to possess oncogenic potential on its own, and activation of Stat3 signaling is required for HGF/c-Met-mediated tumorigenesis. In this study, we examined the correlation between Stat3 activation and HGF/c-Met signaling in samples of oral squamous cell carcinoma (OSCC). Immunohistochemical examination revealed the phosphorylated form of Stat3 in the nuclei of 62/84 OSCC tissue samples but not in normal mucosa, while c-Met expression was detected in 48 samples. Approximately half of the c-Met positive samples also contained phospho-Stat3. There were highly significant correlations between activation of Stat3 and c-Met expression (p=0.00097) and tumor stage. These results indicate that activation of Stat3 mediated by c-Met is frequently associated with the progression of OSCC.
Klosek
Sebastian Krystian
SK
Department of Oral and Maxillofacial Surgery, Ehime University School of Medicine, Ehime 791-0295, Japan.
Nakashiro
Koh-ichi
K
Hara
Shingo
S
Li
Chunnan
C
Shintani
Satoru
S
Hamakawa
Hiroyuki
H
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D019859:Proto-Oncogene Proteins c-met