Integrin signaling group
Head: Daniel Rösel
Prague node
HOME INSTITUTION
Faculty of Science CU
RESEARCH PROGRAMME(S)
RP 1 - Molecular basis of cancer and molecular targets
Basic research is the engine of applied research.
- Mission: To elucidate of molecular mechanisms of tumor transformation and invasive properties of tumor cells.
- Vision: Identify and therapeutically target molecular mechanisms responsible for metastasis.
Integrins are bidirectional transmitters of biochemical signals and mechanical force between the cytoskeleton and the ECM. Interactions between integrins and ECM components initiate signal transduction pathways that regulate cell proliferation, differentiation, and movement. Therefore, deregulation of integrin signaling is frequently associated with the initiation, progression, and metastasis of solid tumors. Because integrins lack enzymatic activity, their signaling is mediated by an indirect mechanism involving integrin clustering that leads to the recruitment and activation of associated kinases such as Src and scaffolding molecules, such as p130CAS. The Integrin signaling group studies various aspects of integrin signaling, focusing on the regulation of the proto-oncogene c-src, the structure and dynamics of cancer cell adhesion structures, and mechanosignaling mediated by Src kinase and adaptor protein p130CAS.
SELECTED PUBLICATIONS
- Škarková A, Bizzarri M, Janoštiak R, Mašek J, Rosel D, Brábek J. Educate, not kill: treating cancer without triggering its defenses.Trends Mol Med. 2024 Apr 23:S1471-4914(24)00091-1. DOI: 10.1016/j.molmed.2024.04.003
- Koudelková L, Pelantová M, Brůhová Z, Sztacho M, Pavlík V, Pánek D, Gemperle J, Talacko P, Brábek J, Rösel D. Phosphorylation of tyrosine 90 in SH3 domain is a new regulatory switch controlling Src kinase. Elife. 2023 Jul 10;12:e82428. DOI: 10.7554/eLife.82428
- Koudelková L, Pataki AC, Tolde O, Pavlik V, Nobis M, Gemperle J, Anderson K, Brábek J, Rosel D. Novel FRET-Based Src Biosensor Reveals Mechanisms of Src Activation and Its Dynamics in Focal Adhesions. Cell Chem Biol. 2019 Feb 21;26(2):255-268.e4. DOI: 10.1016/j.chembiol.2018.10.024
- Rosel D, Fernandes M, Sanz-Moreno V, Brábek J. Migrastatics: Redirecting R&D in Solid Cancer Towards Metastasis? Trends Cancer. 2019 Dec;5(12):755-756. DOI: 10.1016/j.trecan.2019.10.011
- Janoštiak R, Brábek J, Auernheimer V, Tatárová Z, Lautscham LA, Dey T, Gemperle J, Merkel R, Goldmann WH, Fabry B, Rösel D. CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics. Cell Mol Life Sci. 2014 Feb;71(4):727-44. DOI: 10.1007/s00018-013-1450-x
COLLABORATION WITHIN THE NICR
Aleksi Šedo
(Prague node, First Faculty of Medicine CU)
Jan Brábek
(Prague node, Faculty of Science CU)
Jaroslav Truksa
(Prague node, Institute of Biotechnology of the Czech Academy of Sciences)
Karel Smetana
(Prague node, First Faculty of Medicine CU)
Michal Kolář
(Prague node, Institute of Molecular Genetics of the Czech Academy of Sciences)
Vladimír Kryštof
(Olomouc node, Faculty of Medicine PU in Olomouc)
SPECIALIZED EXPERTISE AND TECHNOLOGY
Advanced fluorescence microscopy, FRET, traction force microscopy
Advanced live cell imaging with a focus on analyses related to cell migration and invasiveness in 2D and 3D environments
Biochemical analysis of kinases, protein-protein interactions
COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES
National infrastructure for biological and biomedical imaging Czech-Bioimaging
Biotechnology and Biomedicine Centre of the Czech Academy of Sciences and the Charles University BIOCEV
Central European Institute of Technology at Brno University of Technology CEITEC VUT