Instytut Biologii Medycznej PAN

Labs > Molecular and Cellular Biology > Currently ongoing projects

Currently ongoing projects


 

  1. NCN: DEC-2019/35/D/NZ5/00558 (SONATA): The evaluation of SNAIL 1 and SNAIL 2 transcriptional factors' role in the development of ovarian cancer cells' chemoresistance in regard to their invasiveness. 2020 – 2023
    Principal Investigator: Michał Kiełbik, PhD

 

Despite significant improvements in conventional therapies and patient treatment, high resistance of ovarian cancer cells to platinum compounds (standard chemotherapeutic agents) remains main clinical problem. Another important factor reducing the effectiveness of patients’ treatment is enhanced invasive potential of ovarian cancer cells and creation of metastases. Simultaneous occurrence of chemoresistance and ability to create metastases, significantly reduces the effectiveness of most conventional therapies. The pivotal process contributing to cancer dissemination and migration is epithelial-mesenchymal transition (EMT). The incidence of EMT in turn is modulated by various transcriptional factors known as “master regulators”, among which the most essential ones seems to be those belonging to SNAIL, TWIST and ZEB families. It is well known that SNAIL transcription factors play pivotal role in cancer progression. Latest research suggest that they may also have implication in ovarian cancer chemoresistance. The main goal of this project is to fully clarify the role of transcription factors belonging to SNAIL family, along with the mechanisms of their regulation, in development and sustainment of chemoresistance in ovarian cancer cells in regard to their metastatic potential. The study will be conducted with the use of commercially available ovarian cancer cell lines: cisplatin-sensitive A2780 and cisplatin-resistant A2780cis and SK-OV-3. Moreover, epithelial ovarian cancer (EOC) cells isolated from tumor and ascites fluids from patients, as well as primary EOC cultures will be used. The experiments performed in the course of this project will focus on evaluation of SNAI1 and SNAI2 expression, as well as SNAIL 1/2 protein level, activity and their cellular localization. Moreover, various inhibitors of STAT3 and AKT activity will be used in order to evaluate the impact of these kinases on the development of SNAIL-mediated chemoresistance and invasiveness in ovarian cancer. The results of this project will definitely systemize and broaden the knowledge regarding the sequence in which chemoresistance and invasiveness occur in ovarian cancer and the involvement of SNAIL transcription factors in the induction of these events.

Labs > Molecular and Cellular Biology > Currently ongoing projects