AP-1: Its role in gastrointestinal malignancies

Abstract

The role of transcription factor AP-1 (activator protein 1) in human physiology is distinct due to its involvement in tissue regeneration in which the metabolism is instigated by the signals which trigger undifferentiated proliferative cells to proceed toward cell differentiation. Consequently the functions of AP-1 may be altered in response to extracellular signals. The studies on gene-knockout mice and AP-1-deficient cell lines propose that AP-1 regulates multiple gene targets and accomplishes accurate physiological functions. There is a significant breakthrough in unveiling the molecular mechanisms and signaling pathways that monitors AP-1 activity. AP-1 functions as a double-edged sword in cancer progression through monitoring gene expression involving cell proliferation, cellular differentiation, cell death, and tumor invasion. AP-1 can be oncogenic and antioncogenic too. The activities of AP-1 in cancer appear to rely on composition of AP-1 dimers and type, stage, and genetic basis of cancer. c-Jun protein, one of the subunits of AP-1 up on activation, is expressed primarily at invasive front in carcinomas leading to the proliferation of malignant cells. Thus, c-Jun mainly has oncogenic functions, while JunB and JunD have antioncogenic effects. AP-1‘s role is being studied not only in cancers but also in disorders such as psoriasis, asthma, and transplant rejection. AP-1 emerged as drug discovery target in recent years. This review is being structured to highlight the role of AP-1 transcription factor in the gastrointestinal malignancy progression.