The role of JAK/STAT signaling pathway and TNF-α crosstalk in human colorectal cancer

Abstract

Colorectal cancer (CRC) constitutes a significant portion of mortality and morbidity due to cancer around the world. The present study was designed to evaluate the possible effects of the JAK/STAT, TNF-α, and NFκB pathways, and the caspase-3 apoptotic marker in human colorectal tissue. Data from tumor tissue and adjacent normal colon tissue (n:12) were obtained. Given the biological role of the JAK/STAT signaling pathway in human colorectal tissue, we evaluated interactions with TNFα, NFκB, and caspase-3. We measured the mRNA levels of STAT1, TNF-α, TNF-α R1A, NFκB, and caspase-3 by RT-PCR. The STAT1, TNF-α, TNF-α R1A, and NFκB mRNA levels were increased in colorectal cancer tissue compared to adjacent normal colon tissue (P<0.01, P<0.05, P<0.05, and P<0.05, respectively). There were no significant differences between colorectal cancer and adjacent normal colon tissue regarding the caspase-3 mRNA levels. STAT1 contributes to oncogenesis by promoting the progression of the cell cycle and preventing cells from undergoing apoptosis. In addition, TNF-α has proangiogenic activity and increases the neovascularization of tumors. According to our results, the mRNA levels of STAT1 and TNF-α were significantly higher in cancer tissues, but the mRNA levels of the apoptotic genes caspase-3 and 9 were similar to those of the normal colon tissue, suggesting that STAT1 and TNF-α are important components in the progression of colorectal cancer. These data support the importance of the JAK/STAT signaling pathway in colorectal cancer and suggest targets for intervention. We will be investigating potentially related genes, pathways, and interactions in our future studies.