pCancer and FOXK2 (Forkhead Box K2): Oncogenic and Tumor-Suppressive Roles of FOXK2 in Cancer

Cancer is the second leading cause of death in both developed and developing countries. In cancer cells, hemostasis is disrupted, a process that is maintained under normal conditions in healthy cells. Transcription factors that play a crucial role in preserving this hemostasis have been linked to cancer. In recent years, the involvement of proteins from the FOX transcription factor family in cancer development has been extensively studied, highlighting their potential relevance for therapeutic research. Although one of these proteins, Forkhead Box K2 (FOXK2), was identified in the early 1990s, its biological functions in cellular processes remain incompletely understood. Research has highlighted the roles of FOXK2 in critical molecular processes, including de novo nucleotide synthesis, the expression of metabolic-related enzymes, DNA mismatch repair, cell proliferation, differentiation, apoptosis, and autophagy. Furthermore, it has been shown that FOXK2 mediates the binding of transcription factors that do not directly interact with methylated DNA to methylated regions, and also influences the DNA methylation process. Studies investigating its role in cancer indicate that FOXK2 functions as an oncogenic in certain tissues while acting as a tumor suppressor in others. The role of FOXK2 is particularly controversial, especially in hormone-dependent diseases. In this review, the roles of FOXK2 in various cancer cell types were analysed. Additionally, Gene Ontology (GO) enrichment analyses of miRNAs targeting FOXK2 were conducted, highlighting aspects of FOXK2 that have yet to be explored. GO analysis revealed that miRNAs targeting FOXK2 are particularly involved in regulatory processes. In conclusion, FOXK2 may represent a potential therapeutic target in certain cancer types, although its context-dependent roles require further investigation.