Steering of carcinoma progression by the YIN/YANG interaction of STAT1/STAT3.

STAT1/STAT3 transcription factors are important regulators for development of normal, infected or inflammed cells. They are also critically involved in the progression of various malignant tumours, including epithelial-derived carcinomas. Here, we focus on colorectal cancer (CRC) insights for STAT1/3, where controversial functions for STAT3 were reported. For a long time STAT3 has been regarded as a driver of tumour malignancy and its activation was associated with negative clinical outcome. In contrast, STAT1 was generally viewed as an independent tumour suppressor and positive prognostic marker. Here we discuss the experimental evidence for the tight association and regulation of oncogenic STAT3 transcription kept at bay by nuclear STAT1. We summarise current research and describe cellular models of different STAT1/STAT3 expression ratios. STAT1/3 expression levels are influenced by the mutational status of carcinoma cells associated with nuclear unphosphorylated STAT1. Animal tumour models and results from in vitro experiments allow for the conclusion that both proteins interact as antagonistic transcription factors in CRC cells. These STATs steer also important processes during infection and inflammation that influence development and progression of CRC. The STAT1/3 interplay is important to understand gene regulation and we describe it here similar like the YIN/YANG dualism. Thus, we propose to evaluate both STAT1 and STAT3 expression patterns in cancers in a dual manner instead of regarding them as independent transcription factors. This conceptual dualistic view could advance diagnostic predictions in the future.

Peking Union Medical College Hospital
Jena Univ Hosp
Minist Hlth
Chinese Academy of Medical Sciences
Medizinische Universität Wien - AKH
Ludwig Boltzmann Institut für Krebsforschung
Veterinärmedizinische Universität Wien
Cincinnati Children's Hospital Medical Center