CANCER PLASTICITY

Unraveling the secrets of tumor cell plasticity

Mgr. Karel Souček, Ph.D.

Research focus
The major research interest is to understand the plasticity and heterogeneity of cancer cells and the role of the microenvironment in cancer progression. Cellular plasticity has been considered as a factor con­tributing to the resistance to cancer chemotherapy and poor prognosis. Simultaneously, recurrence and chemoresistance of many types of cancers are believed to be tightly linked with the biology of cancer stem-like cells or tumor-initiating cells (CSCs/TICs) and circulating tumor cells (CTCs). There is increasing evidence that cancer plasticity induced by different stimuli is a source of CSCs/TICs/CTCs. Currently, we have identified in vitro and in vivo experimental models showing heterogeneity in cancer cell plasticity in terms of CSC and the plasticity profile. We are characterizing single cells and single cell-derived clones to understand molecular mechanisms associated with cell plasticity and its role in cancer progression, therapy resistance and the generation of the cells with CSCs/TICs/CTCs-like properties.

Research objectives

• Correlation between the plasticity of cancer cells with aberrant signaling, dissemination capability and chemoresistance.

• Description of heterogeneity of expression of markers defining most aggressive cells at single cell level within a tumor.

• Introducing the methods for expansion and characterization of clinical samples maintaining its original phenotype (e.g. patient-derived xenografts, 3D in vitro cultures of organoids/tumoroids).

Main partners

• Institute of Biophysics, Czech Academy of Sciences, Brno, Czech Republic

• Masaryk University, Faculty of Science & Faculty of Medicine, Brno Czech Republic

• Masaryk Memorial Cancer Institute, Brno, Czech Republic

• Palacky University Olomouc, Faculty of Medicine & University Hospital Olomouc, Czech Republic

• Medical University of Innsbruck, Innsbruck, Austria

• Leiden University Medical Centre, Leiden, Nederland

• Karolinska Institutet, Stockholm, Sweden

• University of Zurich, Zurich, Switzerland

• University College Dublin, Dublin, Ireland

Offered services and expertise

• Complex analysis of cytokinetics – analysis of proliferation, differentiation and cell death using a variety of methods and approaches including single cell analysis techniques.

• Real-time analysis of cell energy metabolism.

• Pre-clinical in vivo imaging of tumor progression using immunodeficient mice.

• Targeted gene knock-out methodology.

Top publications

  • Drápela, S., Khirsariya, P., Van Weerden, W.M., Fedr, R., Suchánková, T., Búzová, D., Červený, J., Hampl, A., Puhr, M., Watson, W.R., Culig, Z., Krejčí, L., Paruch, K., and Souček, K. The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel-resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe. Molecular Oncology. 2020
  • Remšík J, Binó L, Kahounová Z, Kharaishvili G, Šimecková Š, Fedr R, Kucírková T, Lenárt S, Muresan XM, Slabáková E, Knopfová L, Bouchal J, Král M, Beneš P, Soucek K. Trop-2 plasticity is controlled by epithelial-to-mesenchymal transition. Carcinogenesis. 2018: 39, 1411-1418.
  • Knopfová L, Biglieri E, Volodko N, Masařík M, Hermanová M, Glaus Garzón JF, Dúcka M, Kučírková T, Souček K, Šmarda J, Beneš P, Borsig L.Transcription factor c-Myb inhibits breast cancer lung metastasis by suppression of tumor cell seeding. Oncogene. 2018; 37: 1020-1030.
  • Verlande A, Krafčíková M, Potěšil D, Trantírek L, Zdráhal Z, Elkalaf M, Trnka J, Souček K, Rauch N, Rauch J, Kolch W, Uldrijan S. Metabolic stress regulates ERK activity by controlling KSR-RAF heterodimerization. EMBO Rep. 2018; 19: 320-336.
  • Samadder, P., Suchankova, T., Hylse, O., Khirsariya, P., Nikulenkov, F., Drapela, S., Strakova, N., Vanhara, P., Vasickova, K., Kolarova, H., Bino, L., Bittova, M., Ovesna, P., Kollar, P., Fedr, R., Esner, M., Jaros, J., Hampl, A., Krejci, L., Paruch, K., and Soucek, K. Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation. Molecular Cancer Therapeutics. 2017; 16, 1831-1842.

Other selected results

Collaboration with Contripro and PrimeCell companies.

Total number of defended PhD students within the team (2011-2020): 11

Total number of defended M.Sc. studends within the team (2011-2020): 25