Expression of FOXP3 gene as the risk-factor of metastasis development

Scientific Investigator: Ekaterina Kldiashvili Project Investigator: 2019-03-18 Project Duration: 6 months

Project has been realized by participation of students registered for the teaching course "Biochemistry 3".
Oncology diseases and their treatment are the priority tasks of healthcare. The cancer critical genes are already determined, but genes responsible for development of metastasis and cancer recurrence are not identified till present.
FOXP3 (Forkhead box protein P3) gene is one of the candidates. The expression of the mentioned gene in tumor cells has been determined experimentally (Ebert et al., 2008; Karanikas et al., 2008; Takenaka et al., 2013). FOXP3 gene is located in the short arm of X chromosome. It is coding transcription factor and is characterized by the complicated mechanism of gene expression. FOXP3 gene’s expression in tumor cells ensures the development of immunosuppression (Hinz et al., 2007; Cuncha et al., 2012; Waight et al., 2015) through the transformation of regulatory T cells to Tregs (Liyanage et al., 2006; Li et al., 2007; Yuan et al., 2011). It is known, that presence of Tregs in tumor tissue is associated with poor prognosis (Adeegbe et al., 2013; Ondondo et al., 2013; Sahin et al., 2013).
The intensive expression of SOX2 and OCT4 genes in tumor cells is also important from the point of molecular mechanisms of metastasis (Xu et al., 2017; Ayob et al., 2018). These genes belong to the group of genes specific to stem cells. They are coding transcription factors those activity is important for embryonal development and formation of different tissues. Therefore, expression of SOX2 and OCT4 genes in tumor tissue correlates with the concept of cancer stem cells. Accordingly with this concept neoplastic growth is similar to the renewal of normal tissue and is ensured by stimulation of cancer stem cells. Furthermore, the presence of cancer stem cells in tumor tissue has been determined experimentally (Batle, 2017).
Taking into account all above mentioned, we propose that intensive expression of FOXP3 gene is the molecular pre requisite of metastasis development and ensures activation of SOX2 and OCT4 genes.
The aim of the proposal is experimental provement of the above mentioned scientific hypothesis.