Molecular and Cellular Mechanisms of Invasiveness of Tumour Cells

Molecular and Cellular Mechanisms of Invasiveness of Tumour Cells

Doc. RNDr. Jan Brábek, Ph.D.

Doc. RNDr. Jan Brábek, Ph.D. — Project head

About us

This project is focused on functional analysis of mesenchymal and amoeboid invasiveness of tumour cells. The main areas of interests are molecular mechanisms related to structures and turnover of podosomes and invadopodia and the molecular mechanisms of Rho/ROCK pathway activation in amoeboid tumour cells. The research provides potential for development of new anti-metastatic strategies.

Objectives:

  • Determination of the role of integrin-associated Src substrates for mesenchymal tumour cell invasiveness
  • Search for proteins responsible for activation of the Rho/ROCK pathway in amoeboid tumour cells

 

Our team is investigating molecular and morphological processes required for the successful invasion of cancer cells and the molecular aspects of cell transformation. We discovered amoeboid invasiveness as a primary mode of invasion in mesenchymal (sarcoma) cancer cells and at the same time we directly correlated the up-regulation of Rho/ROCK signaling in amoeboid invasiveness with greater capability to generate a protrusive force at the leading edge (Rösel et al., 2008) and brought the best evidence for amoeboid metastasis in vivo (Kosla et al., 2013). We were the first to describe the morphology of invadopodia in a complex 3D environment (Tolde et al., 2010).

We also proved the existence of focal adhesions in a complex 3D environment and showed they are of a comparable size and dynamics as focal adhesions in 2D (Tolde et al., 2012). Recently, we have proved the role of CAS SH3 domain tyrosine phosphorylation in the migration and invasiveness of Src-transformed cells (Janostiak et al., 2011) and the role of the newly-discovered direct CAS-vinculin interaction in mechanosensing (Janostiak et al., 2014). We also uncovered the role of tyrosine phosphorylation within SH3 domains as a novel general regulatory mechanism for cell signaling (Tatárová et al., 2012)

 

Potential for cooperation

We are members of the Invadosome Consortium and benefit from our collaboration with laboratories within the Consortium as well as many other national and international joint projects. We are able to offer to those with whom we work our expertise in quantitative analyses of cancer cell invasion in 30 collagen, including the vertical invasion assay and outgrowth of cell spheroids, in addition we can offer analyses of invasive behaviour on a unique life-like matrix - acellular dermis. We can also offer analyses of cell signaling after mechanical stretching on our cell stretcher.

More info

News

Publications

2018
2017
2016

Gandalovičová A, Vomastek T, Rosel D, Brábek J.Cell polarity signaling in the plasticity of cancer cell invasiveness. Oncotarget. 2016 May 3;7(18):25022-49. doi: 10.18632/oncotarget.7214. Review.

Jobe NP, Rösel D, Dvořánková B, Kodet O, Lacina L, Mateu R, Smetana K, Brábek J. Simultaneous blocking of IL-6 and IL-8 is sufficient to fully inhibit CAF-induced human melanoma cell invasiveness. Histochem Cell Biol. 2016 Aug;146(2):205-17. doi: 10.1007/s00418-016-1433-8. Epub 2016 Apr 21.

Brábek J, Rosel D, Fernandes M. Pragmatic medicine in solid cancer: a translational alternative to precision medicine. Onco Targets Ther. 2016 Apr 5;9:1839-55. doi: 10.2147/OTT.S103832. eCollection 2016.

2015

Fernandes M, Rosel D, Brábek J. Translation in solid cancer: are size-based response criteria an anachronism? Clin Transl Oncol. 2015 Jan;17(1):1-10. doi: 10.1007/s12094-014-1207-5. Epub 2014 Jul 30.

Pataki CA, Couchman JR, Brábek J. Wnt Signaling Cascades and the Roles of Syndecan Proteoglycans.J Histochem Cytochem. 2015 Jul;63(7):465-80. doi: 10.1369/0022155415586961. Epub 2015 Apr 24. Review.

Vaškovičová K, Szabadosová E, Čermák V, Gandalovičová A, Kasalová L, Rösel D, Brábek J.PKCα promotes the mesenchymal to amoeboid transition and increases cancer cell invasiveness. BMC Cancer. 2015 Apr 29;15:326. doi: 10.1186/s12885-015-1347-1.

2014

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.

Janoštiak R, Pataki AC, Brábek J, Rösel D. Mechanosensors in integrin signaling: The emerging role of p130Cas. Eur J Cell Biol. 2014 Oct;93(10-12): 445-54

2013

Vaškovičová K, Zárský V, Rösel D, Nikolič M, Buccione R, Cvrčková F, Brábek J (2013). Invasive cells in animals and plants: searching for LECA machineries in later eukaryotic life. Biol Direct. 8:8. doi: 10.1186/1745-6150-8-8. (IF 2.720)

Rösel D, Brábek J, Veselý P, Fernandes M. (2013) Drugs for solid cancer: the productivity crisis prompts a rethink. Onco Targets Ther. Jun 26;6:767-77. (IF = 2.073)

Kosla J, Paňková D, Plachý J, Tolde O, Bicanová K, Dvořák M, Rösel D, Brábek J. Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling. Cell Commun Signal. 2013 Jul 30;11(1):51. doi: 10.1186/1478-811X-11-51.

Team

Doc. RNDr. Jan Brábek, Ph.D.

Doc. RNDr.
Jan Brábek, Ph.D.

Head of Group Molecular and Cellular Mechanisms of Invasiveness of Tumour Cells

jan.brabek@natur.cuni.cz
+420325873900, +420325873902

Mgr.
Vladimír Čermák, Ph.D.

vladimir.cermak@natur.cuni.cz
+420325873937