Project summary

During its life, the cell is exposed to a number of stimuli that indicate a possible threat to its integrity. These stimuli trigger activation of the stress signaling pathways that control the adaptation of the cell to the stimulus or lead to apoptosis. MAP kinases p38 and JNK play a key role in stress signaling, triggering a phosphorylation cascade to regulate effector protein activity in response to extracellular signals. MAPK pathways generally regulate many cellular processes in addition to stress response, such as cell proliferation, differentiation or secretion of various factors. Their role in carcinogenesis is thus not surprising. While their effect on cellular transformation is relatively well studied, less is known about how they regulate the metastasis process, which, however, is responsible for most of cancer deaths. During the invasion of the extracellular space cancer cells use various migration modes, most commonly the collective, amoeboid or mesenchymal mode of migration. The fact that these modes are often interchangeable complicates successful treatment. The influence of MAP kinase pathways on cellular invasiveness has been extensively studied, however, whether they participate in the selection of migration mode has not yet been analyzed. The ability of cancer cells to switch between invasion modes underlies the metastatic disease. Our preliminary results indicate the key role of MAP kinase signaling pathways during individual migration strategies. The aim of this project is to find out how the components of stress-associated MAP kinase signaling pathways contribute to cancer cell invasiveness and how they synergize to drive the metastatic behavior of cancer cells.

Five relevant publications of the research group

Gemperle J, Dibus M, Koudelková L, Rosel D, Brábek J. The interaction of p130Cas with PKN3 promotes malignant growth. Molecular Oncology 2018, doi: 10.1002/1878-0261.12401.

Čermák V, Gandalovičová A, Merta L, Fučíková J, Špíšek R, Rösel D, Brábek J. RNA-seq of macrophages of amoeboid or mesenchymal migratory phenotype due to specific structure of environment. Sci Data. 2018, 5:180198.

Tolde O, Gandalovičová A, Křížová A, Veselý P, Chmelík R, Rosel D, Brábek J. Quantitative phase imaging unravels new insight into dynamics of mesenchymal and amoeboid cancer cell invasion. Sci Rep. 2018, 8(1):12020..

Gandalovičová A, Rosel D, Fernandes M, Veselý P, Heneberg P, Čermák V, Petruželka L, Kumar S, Sanz-Moreno V, Brábek J. MIGRASTATICS-anti-metastatic and anti-invasion drugs: promises and challenges. Trends In Cancer 2017, 3(6):391-406

Fernandes M, Rosel D, Brábek J. Limits to Precision Cancer Medicine.N Engl J Med. 2017 376(1):95-6.

Current research grants of the group

2018-2020 18-15684J The role of matrix metalloproteinases and vimentin cooperation in cancer cell invadopodia function.

2018-2022 Center of Tumor Ecology

Source of financial support of the project
(min. 5000 CZK per month)

Center of Tumor Ecology 'Center for Tumor Ecology – Research of the Cancer Microenvironment Supporting Cancer Growth and Spread' (reg.no. CZ.02.1.01/0.0/0.0/16_019/0000785) supported by the Operational Programme Research, Developmentand Education.