The role of signal transducers and activators of transcription in colon cancer.

A family of latent cytoplasmic transcription factors, Signal Transducers and Activators of Transcription (STATs), convey signals from numerous cytokines and growth factors to the nucleus. Their expression and their activity have been shown to be perturbed in a variety of malignancies, including colorectal cancer. Among the STAT family members, oncogenic STAT3 has been shown to be constitutively activated or overexpressed in colon cancers. In contrast, the expression levels of STAT1 have been found to be reduced in transformed intestinal epithelial cells, consistent with tumor suppressor properties of STAT1. We showed that transformation of intestinal epithelial cells with KRasV12 is sufficient to downregulate the expression of STAT1. Because both STAT1 and STAT3 are important regulators of genes that are involved in cell survival (BCL-x, survivin, caspases) and cell proliferation (c-Myc, p21, cyclin D1), their deregulation significantly impacts the homeostasis of intestinal tissues. The critical role of STATs in oncogenesis and in inflammation merits further investigation of targeted inhibitors of STATs activity that could be used alone or in combination with conventional chemotherapy.