Human embryonic stem (hES) cells are characterised by infinite proliferation and self-renewal capacity. In addition, hES cells are pluripotent, which means they can differentiate into almost every cell of the body. In our research we have focused on the control of their cell cycle and regulation mechanisms of pluripotency.
Another type of cells with infinite proliferation capacity are cancer cells. Previously we have focused on the tumour suppressor protein p53 in cancer cells. In the current project, we aim to uncover the role of aryl hydrocarbon receptor (AHR) in pancreatic ductal adenocarcinoma (PDAC). We test the hypothesis that inhibition of AHR activity with specific inhibitors has a potent therapeutic value in PDAC treatment. It is also important to mention that inhibition of AHR activity has great potential to boost the efficacy of cancer immunotherapy. Together with our project partners, we will develop and test novel AHR inhibitors in preclinical experiments.
Project: Inhibition of AHR signaling in pancreatic cancer to increase susceptibility to PD-1/PD-L1 inhibitors and chemotherapy via ELAVL1 pathway
Project donor: Baltic Research Cooperation Programme
Project timeline: 01.01.2021 - 31.12.2023
Project promoter: Lithuanian University of Health Sciences
More about the project, including the tasks and the overview of the meeting in Kaunas in October 2021.
1. Klepinina, L., Klepinin, A., Truu, L., Chekulayev, V., Vija, H., Kuus, K., Teino, I., Pook, M., Maimets, T. & Käämbre, T. (2021) Colon cancer cell differentiation by sodium butyrate modulates metabolic plasticity of Caco-2 cells via alteration of phosphotransfer network. PLOS ONE, 16(1): e0245348. DOI: 10.1371/journal.pone.0245348
2. Teino, I., Matvere, A., Pook, Martin., Varik. I., Pajusaar, L., Uudeküll, K., Vaher, H., Trei, A., Kristjuhan, A., Org, T. & Maimets, T. (2020). Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation. Int. J. Mol. Sci. 21(23), 9052. DOI: 10.3390/ijms21239052
3. Matvere, A., Teino, I., Varik, I., Kuuse, S., Tiido, T., Kristjuhan, A., & Maimets, T. (2019). FSH/LH-Dependent Upregulation of Ahr in Murine Granulosa Cells Is Controlled by PKA Signaling and Involves Epigenetic Regulation. International Journal of Molecular Sciences, 20, 3068. DOI: 10.3390/ijms20123068
4. Ervin, E. H., Pook, M., Teino, I., Kasuk, V., Trei, A., Pooga, M., & Maimets, T. (2019). Targeted gene silencing in human embryonic stem cells using cell-penetrating peptide PepFect. Stem Cell Research and Therapy, 10:43. DOI: 10.1186/s13287-019-1144-x
5. Ounpuu, L., Klepinin, A., Pook, M., Teino, I., Peet, N., Paju, K., Tepp, K., Chekulayev, V., Shevchuk, I., Koks, S., Maimets, T., & Kaambre, T. (2017). 2102Ep embryonal carcinoma cells have compromised respiration and shifted bioenergetic profile distinct from H9 human embryonic stem cells. Biochimica et Biophysica Acta - General Subjects, 1861, 2146-2154. DOI: 10.1016/j.bbagen.2017.05.020