Physiologically, FoxA1 plays a key role in liver differentiation and development, and pathologically exhibits an oncogenic role in prostate and breast cancers. However, its role and upstream regulation in liver tumorigenesis remain unclear.
On February 7, 2024, Jianping Guo, Lixia Xu, Wei Xie from Sun Yat-sen University, and Ying Liang from Guangzhou Medical University, co-corresponding authors, published a research paper titled "Atypical inflammatory kinase IKBKE phosphorylates and inactivates FoxA1 to promote liver tumorigenesis" online in Science Advances (impact factor: 14.98). This study demonstrated the suppressive role of FoxA1 in liver cancer. Using a CRISPR-based kinome screening approach, they found that the noncanonical inflammatory kinase IKBKE can inhibit FoxA1's transcriptional activity.
It is noteworthy that IKBKE directly binds to and phosphorylates FoxA1, reducing its complex formation and DNA interaction, resulting in an increase in hepatocellular malignancies. Knock-in mice with non-phosphorylated mimic Foxa1 significantly delayed liver tumor occurrence in hydrodynamic transfection murine models, while knock-in mice with phospho-mimic Foxa1 phenocopied Foxa1 knockout mice, exhibiting developmental defects and liver inflammation. Importantly, Ikbke knockout delayed the development of diethylnitrosamine (DEN)-induced liver tumors in mice.
In summary, this study not only reveals FoxA1 as a bona fide substrate and negative nuclear effector of IKBKE in hepatocellular carcinoma (HCC) but also provides a promising strategy to target IKBKE for HCC therapy.
In conjunction with the research study, Biotin end-labeled probe utilized was supplied by SBS Genetech Co., Ltd. Since 2000, SBS Genetech has been at the forefront of providing solutions in life sciences. We offer safer, superior quality, and more cost-effective products to preeminent researchers in nearly 60 countries, empowering them to make new discoveries in biology. Our products have been widely utilized in academic research, with results often published in leading academic journals like Science, Cell, Cancer Cell, and Cell Metabolism. We firmly believe that through continuous innovation and research, we will continually infuse new vitality and possibilities into the field of life sciences.