Constitutive activation of Stat3 correlates with increased expression of the c-Met/HGF receptor in oral squamous cell carcinoma

• DOI: 10.3892/or.12.2.293
• Publication Date: 2014-03-10T07:47:13Z
• Authors: Sebastian Klosek; Koh-Ichi Nakashiro; Shingo Hara; Chunnan Li; Satoru Shintani; Hiroyuki Hamakawa
• Keywords: Adult; Cell Nucleus; Male; STAT3 Transcription Factor; Mouth Mucosa; Middle Aged; Proto-Oncogene Proteins c-met; Immunohistochemistry; DNA-Binding Proteins; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Lymphatic Metastasis; Carcinoma, Squamous Cell; Disease Progression; Trans-Activators; Humans; Female; Mouth Neoplasms; Phosphorylation

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.