Stat3 activation is required for cell proliferation and tumorigenesis but not for cell viability in cutaneous...

Signal transducer and activator of transcription 3 (Stat3), a cytoplasmic transcription factor, is constitutively activated in various types of cancer. Previous investigations have demonstrated that Stat3 plays important roles in cell growth, survival, differentiation, and transformation. The constitutive activation of Stat3 in human malignancies is an important key to maintain the characteristics of a malignant tumor, such as the rate of proliferation and/or immortalization, and inhibition of Stat3 function could be a potent therapeutic approach. In order to elucidate the role of Stat3 in tumors, cutaneous squamous cell carcinoma (SCC) cells, which have constitutive activation of Stat3 in vivo and in vitro, were used for this study. To investigate the effect of specific inhibition of Stat3 in SCC cells, we developed small interfering RNAs (siRNAs) that target Stat3, and which effectively prevent its expression in vitro. Introduction of Stat3 siRNA into SCC cells led to inhibition of growth and changes in morphology but did not induce apoptosis. Stat3 siRNA-transfected SCC cells had impaired tumor growth in nude mice. These findings demonstrate that Stat3 plays a critical role in the tumorigenesis, but not in the cell survival, of SCC cells and suggest that additional pro-apoptotic signals are necessary for the induction of apoptosis.