Cancer cells are not all the same. There are cells, known as cancer stem cells CSCs, which are resistant to conventional therapies and keep dividing, being responsible for tumor recurrence. The team has been giving much attention to the study of SOX2 transcription factor and has robust biological and clinical data, pointing SOX2 as a protein important in the gastric and intestinal cancer progression and in resistance to therapy. The goal of this project is to identify other transcription factors that, together with SOX2, are fundamental to the formation of CSCs. By knowing these factors, strategies can be invisioned to reduce the viability of CSCs and to better predict the survival of patients with cancer, ultimately improving diagnosis and therapy. The team has identified a number of transcription factors associated with SOX2 which will be validated in gastric and colorectal carcinoma cell lines and tumor samples, analysing their co-expression with SOX2. In parallel, an innovative technique will be used to disclose the regulatory regions that are active in single cells isolated from tumors which will reveal the regulatory factors associated with SOX2. The integration of these results will lead to a more refined list of TFs that, in combination with SOX2, will be used to program gastric and intestinal CSCs. For this, pools of candidate TFs will be introduced into SOX2-negative cells and then sequentially removed to identify the minimal combination that is necessary and sufficient to generate CSC. These factors will be used as therapeutic targets for the future, in an attempt to improve the prognosis of patients with cancer. This project represents a collaborative effort between the IPATIMUP/i3S and CNC/UC-Biotech, in which the combination of tools and knowledge of the two teams is a unique opportunity to explore the molecular signalling pathways that sustain CSCs in gastric and intestinal tumors.
|Effective start/end date||1/07/18 → 31/12/21|
- Fundação para a Ciência e a Tecnologia: $282,965.00