Research focus

Major research interest of Cancer Plasticity group is to understand the plasticity and heterogeneity of cancer cells and the role of tumor microenvironment in regulation of cancer progression. Cellular plasticity has been considered as a factor contributing to resistance to cancer chemotherapy and poor prognosis. At the same time, recurrence and chemoresistance of many type of cancers are believed to be strongly connected 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 identified in vitro and in vivo experimental models showing heterogeneity cancer cell plasticity in the term of CSC and plasticity profile. We are analyzing phenotypic characteristics of single cells or single cell-derived clones with the aim to understand better molecular mechanisms associated with cell plasticity and its role in cancer progression and generation of the cells with CSCs/TICs/CTCs-like properties.

Research objectives

  • Correlation of the plasticity of cancer cells with aberrant signaling in cancer cells, dissemination capability and chemoresistance.
  • Description of heterogeneity of expression of markers defining most aggressive cells at single cell level within tumor.
  • Introducing the methods for expansion of clinical samples maintaining its original phenotype (e.g. patient-derived xenografts, 3D in vitro cultures of organoids/tumoroids).

Main partners

  • Medical University of Innsbruck, Innsbruck, Austria
  • Leiden University Medical Centre, Leiden, Nederland
  • Karolinska Institutet, Stockholm, Sweden

Technological equipment

  • Pre-clinical in vivo Imaging System – analysis of tumor progression and therapy response in small experimental animals
  • Real-Time Cell Analysis Systems – label free analysis of cell proliferation/cytotoxicity, differentiation, adhesion, migration and invasion
  • Widefield High-Content Analysis System – automated microscope for multiparametric fluorescent cell analysis in 2D and 3D culture

Offered services and expertise

  • Complex analysis of cytokinetics – analysis of proliferation, differentiation and cell death using variety of methods and approaches including single cell analysis techniques.
  • Pre-clinical in vivo imaging of tumor progression using immunodeficient mice.

Top publications

  • SLABÁKOVÁ, E., KHARAISHVILI, G., SMEJOVÁ, M., PERNICOVÁ, Z., SUCHÁNKOVÁ, T., REMŠÍK, LERCH, S., STRAKOVÁ, BOUCHAL, J., KRÁL, M., CULIG, Z., KOZUBÍK, A., SOUČEK, K. Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells. Oncotarget. 2015, 6(34), 36156-36171.
  • KRATOCHVÍLOVÁ, K., HORAK, P., EŠNER, M., SOUČEK, K., PILS, D., ANEES, M., TOMASICH, E., DRÁFI, F., JURTÍKOVÁ, V., HAMPL, A., KRAINER, M., VAŇHARA, P. Tumor suppressor candidate 3 (TUSC3) prevents the epithelial-to-mesenchymal transition and inhibits tumor growth by modulating the endoplasmic reticulum stress response in ovarian cancer cells. International Journal of Cancer. 2015, 137(6), 1330-1340.
  • PERNICOVÁ, Z., SLABÁKOVÁ, E., FEDR, R., ŠIMEČKOVÁ, Š., JAROŠ, J., SUCHÁNKOVÁ, T., BOUCHAL, J., KHARAISHVILI, G., KRÁL, M., KOZUBÍK, A., SOUČEK, K. The role of high cell density in the promotion of neuroendocrine transdifferentiation of prostate cancer cells. Molecular Cancer. 2014, 13(1), 113.
  • PERNICOVA, Z., SLABAKOVA, E., KHARAISHVILI, G., BOUCHAL, J., KRAL, M., KUNICKA, .Z, MACHALA, M., KOZUBIK, A., SOUCEK, K.Androgen depletion induces senescence in prostate cancer cells through down-regulation of Skp2. Neoplasia. 2011, 13, 526-536.
  • SOUCEK, K., KAMAID, A., PHUNG, A.D., KUBALA, L., BULINSKI, J.C., HARPER, R.W., EISERICH, J.P. Normal and prostate cancer cells display distinct molecular profiles of alpha-tubulin posttranslational modifications. The Prostate. 2006, 66, 954-965.

Other selected results

  • Context dependent regulation of MDM2 expression - Multiple cancer treatment strategies concentrate on MDM2 and MDMX as important regulators of p53-mediated anti-tumor response. We provide evidence to support an alternative and context-specific role of MDM2 in the regulation of cancer cell plasticity, encompassing the phenomena of epithelial-mesenchymal transition, cell migration, and metastasis. These observations can be extrapolated to clinically valuable findings to support appropriate targeting of MDM2 in cancer.
  • Heterogeneity and plasticity of prostate cancer cells - Tumor heterogeneity and the plasticity of cancer cells present challenges for effective clinical diagnosis and therapy. Such challenges are epitomized by neuroendocrine transdifferentiation (NED) and the emergence of neuroendocrine-like cancer cells in prostate tumors. Our results imply a new relationship between high cell density-induced cell cycle attenuation and promotion of NED and suggest high cell density as a trigger for intracellular signaling that can mediate reversible NED in prostate cancer cells. This may help to understand the role of tumor tissue environment and its plasticity.

Team members

  • doc. Mgr. Petr Beneš, Ph.D.
  • Mgr. Karel Souček, Ph.D.
  • Mgr. Stjepan Uldrijan, CSc.
  • Kateřina Svobodová
  • Zoran Culig, MD
  • Mgr. Stanislav Drápela
  • Mgr. Monika Dúcka
  • Mgr. Radek Fedr
  • Mgr. Jitka Glossová
  • Mgr. Barbora Kvokačková
  • Ximena Maria Muresan, Ph.D.
  • Mgr. Jarmila Navrátilová, Ph.D.
  • Mgr. Veronika Palušová
  • Mgr. Markéta Pícková
  • Mgr. Tereza Suchánková, Ph.D.
  • MVDr. Nina Tokanová
  • Mgr. Filip Trčka, Ph.D.
  • Mgr. Ondřej Vacek
  • Ing. Natália Vadovičová
  • Mgr. Barbora Valčíková
  • Ladislava Vymětalová, Ph.D.

Principal Investigator

Mgr. Karel Souček, Ph.D.
Mgr. Karel Souček, Ph.D.
Principal Investigator