SELENOF, previously known as SEP15, is a selenoprotein containing selenocysteine. It belongs to a new family of thioredoxin-like proteins and likely plays a role in redox protein quality control, as well as in the regulation of lipids, glucose, and energy metabolism [1]. Genetic models, such as gene knockout, can be used to study its functions.

Loss of SELENOF contributes to the development of prostate and breast cancer [1,2,3,5]. In prostate cancer, reducing SELENOF in epithelial cells leads to features of the transformed phenotype, including the ability to grow in soft agar, increased migration, and altered energy metabolism [5]. In breast cancer, SELENOF mRNA is lower in late-stage tumors, and its loss affects cell viability, proliferation, and cell death, acting as a tumor suppressor [2,3]. Conversely, in colon cancer, its loss may be protective [1]. Also, in the context of selenium supranutrition, SELENOF-mediated AKT1-FOXO3a-PYGL axis contributes to glycogenolysis and lipogenesis [4].

In conclusion, SELENOF is essential for maintaining normal physiological functions related to metabolism and redox protein quality control. Through gene knockout models, its role in cancer, especially in prostate and breast cancer, has been revealed. These findings provide insights into the potential mechanisms of cancer development and suggest SELENOF as a possible target for cancer treatment and prevention.

References:

1. Flowers, Brenna, Bochnacka, Oliwia, Poles, Allison, Diamond, Alan M, Kastrati, Irida. 2023. Distinct Roles of SELENOF in Different Human Cancers. In Biomolecules, 13, . doi:10.3390/biom13030486. https://pubmed.ncbi.nlm.nih.gov/36979420/

2. Zigrossi, Alexandra, Hong, Lenny K, Ekyalongo, Roudy C, Diamond, Alan M, Kastrati, Irida. 2022. SELENOF is a new tumor suppressor in breast cancer. In Oncogene, 41, 1263-1268. doi:10.1038/s41388-021-02158-w. https://pubmed.ncbi.nlm.nih.gov/35082382/

3. Ekyalongo, Roudy C, Flowers, Brenna, Sharma, Tanu, Singh, Kanishka, Kastrati, Irida. 2023. SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells. In Cancers, 15, . doi:10.3390/cancers15143671. https://pubmed.ncbi.nlm.nih.gov/37509331/

4. Zhang, Dian-Guang, Zhao, Tao, Xu, Xiao-Jian, Jiang, Ming, Luo, Zhi. 2022. Selenoprotein F (SELENOF)-mediated AKT1-FOXO3a-PYGL axis contributes to selenium supranutrition-induced glycogenolysis and lipogenesis. In Biochimica et biophysica acta. Gene regulatory mechanisms, 1865, 194814. doi:10.1016/j.bbagrm.2022.194814. https://pubmed.ncbi.nlm.nih.gov/35439639/

5. Hong, Lenny K, Kadkol, Shrinidhi, Sverdlov, Maria, Liu, Li, Diamond, Alan M. 2021. Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells. In International journal of molecular sciences, 22, . doi:10.3390/ijms222112040. https://pubmed.ncbi.nlm.nih.gov/34769469/