IFN-α competes with TNF-α for STAT-1α; molecular basis for immune escape of human colon adenocarcinoma COLO 205 cells

Abstract

The resistance of transformed colon epithelial cells to immune system-mediated extrinsic apoptosis allows the development of fast growing colon cancer. Several tactics have been shown to clarify how colon adenocarcinomas avoid cell deletion and remain viable. Regardless of the presence of active membrane receptors, colorectal cancer cells resist interferon-mediated cell death. Similarly, they are refractory to TNF-α-dependent apoptosis. In our studies, we assumed that IFN-R and TNF-R1 receptors compete for STAT-1α kinase. Western blot and immunoprecipitation analyses were used to evaluate the protein to protein interactions. Cell viability was measured by MTT assay. We observed that STAT-1α kinase is bound to TRADD protein in TNF-R1 signalosome irrespective of the TNF-R1 bound ligand. The amount of STAT-1α kinase associated with TRADD was diminished after pretreatment with IFNs. IFN-α stimulated the survival of COLO 205 cells rather than promoted cell death. The latter was accompanied by NF-κB activation, a fact known to promote anti-apoptosis. STAT-1α renders colon adenocarcinoma COLO 205 cells less susceptible to TNF-α-induced apoptosis but IFN-α further extends the immune escape.