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Regulation of Epithelial-Mesenchymal transition by the ERK pathway.
Čáslavský, Josef ; Vomastek, Tomáš (advisor) ; Brábek, Jan (referee) ; Gregor, Martin (referee)
Typical epithelium is uniformly polarized solid structure defined by the presence of cell-cell contacts that are connected to well-organized network of actin cytoskeleton. While epithelium is considered to be rather static, during embryogenesis or cancer development epithelial tissues undergo considerable dynamic changes in their integrity that are characterized by loss of epithelial polarity, disruption of cell-cell adhesions and gaining mesenchymal or mesenchymal-like migratory phenotype. These changes, collectively termed as epithelial-mesenchymal transition (EMT), allow cells to effectively invade surrounding tissues and are considered to be a main factor underlying the formation of metastatic cancer. The MAPK/ERK cascade, comprised of protein kinases Raf, MEK and ERK, induces the breakdown of epithelial integrity and cell autonomous migration in various cell lines. In the ERK pathway, ERK is an effector protein kinase which, depending on the cellular context, phosphorylates a number of different substrates. Spatiotemporal phosphorylation of specific constellation of ERK substrates drives specific biologic outcome. The question arises whether, during conversion of multicellular epithelium to autonomously migrating cells, ERK regulates a "master" controller or whether the ERK regulatory function...
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