Studium úlohy proteinkinázy C alfa v améboidní invazivitě nádorových buněk

Vaškovičová, Katarína

1. Abstract Protein kinase C α (PKCα) is a serine/threonine protein kinase regulating many different signaling pathways. The aim of this study was to investigate the potential role of PKCα in amoeboid morphology and invasion of cancer cells. It was observed, that expression of PKCα as well as its phosphorylation on Thr497 remained unchanged upon amoeboid-mesenchymal transition of A375m2 cells (induced by inhibition of ROCK kinase) both in 3D and in 2D environment. However, activation of PKCα by PKC activator treatment resulted in mesenchymal- amoeboid transition of K2 and MDA-MB-231 mesenchymal cell lines, although it did not change overall invasivity ability of cells to invade 3D collagen. Notably, PKCα activation significantly reduced matrix degrading abilities of A375m2 cells. Conversely, inhibition of PKCα by PKCα inhibitor treatment caused amoeboid-mesenchymal transition of amoeboid A375m2 cells and it was associated with decreased invasiveness of all three cell lines used. PKCα inhibitor did not have any effect on gelatin degradation area of A375m2 cells. Consistently, specific siRNA mediated downregulation of PKCα lead to transition from amoeboid to mesenchymal morphology of A375m2 cells and reduced invasiveness of cells into 3D collagen. Moreover, gelatin degrading abilities of A375m2 cells were...

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