Identification of C1qTNF-related protein 4 as a potential cytokine that stimulates the STAT3 and NF-κB pathways and promotes cell survival in human cancer cells

The NF-κB and IL6/STAT3 pathways are major participants in tumor-promoting inflammation. C1qTNF related protein (CTRP) is a family with multiple physiological functions, but their involvement in tumor-promoting inflammation has received little attention. For the first time, we have identified CTRP4 as a novel secretary protein by N-terminal sequencing. Moreover, recombinant CTRP4 can effectively induce the activation of both NF-κB and IL6/STAT3 signaling pathways in the pattern similar to that of classical cytokine. By western blot analysis, we detected the upregulation of CTRP4 in response to IL6. Importantly, functional research revealed that CTRP4 could promote tumor cell survival and tumor resistance against apoptosis induced by chemotherapeutics. These results strongly suggest that CTRP4 is a novel tumor-promoting inflammatory regulator. Our findings might provide a meaningful indication for cancer research.