Increased STAT2 Expression in Colorectal Cancer Cells Enhances Cell Migration and Impairs the Antitumor Effects of Type I Interferons
Nataliya Pryimych and Ana M. Gamero
Temple University, Philadelphia
Disparities in colorectal cancer (CRC) incidence and mortality in racial and ethnic minorities are associated with socioeconomic status, genetic, behavioral and environmental factors. The transcription factor STAT2 plays a key role in driving the antitumor effects of type I interferons (IFNα/β), used as adjuvant cancer therapy that has proven ineffective in CRC. Paradoxically, our studies in animal models of CRC have exposed STAT2 as a tumor promoter. Therefore, we analyzed human CRC datasets in TCGA and discovered colorectal tumors had elevated STAT2 expression that was associated with poor survival. African American and Caucasian CRC patients had in common elevated tumor STAT2 expression. The objective of our study was to investigate the biological significance of high STAT2 in CRC which is unknown. We overexpressed STAT2 in the human carcinoma cell line RKO to mimic elevated tumor STAT2 expression and determine its effects on tumorigenicity. We report STAT2 overexpression provided no growth advantage but enhanced cell motility. Furthermore, the antiproliferative effects of IFN-α were drastically impaired. STAT2 overexpression enhanced IFN-α induced activation of STAT2 and tumorigenic STAT3. Our results indicate that enhanced activation of STAT3 when STAT2 is upregulated may represent a mechanism by which tumor cells become resistant to IFN- α.
Email questions and comments about this abstract to tug44714@temple.edu.
