|
|
Analysis of PKCα Influence on Cancer Cell Invasion.
Szabadosová, Emília ; Brábek, Jan (advisor) ; Nováková, Olga (referee)
7 Abstract Protein kinase C alpha (PKCα) is a serine/threonine protein kinase. PKCα is an important protein regulating cell polarity, protein secretion, apoptosis, cell proliferation and differentiation and tumorogenesis. Previous research has shown a role of PKCα also in a cancer cell migration and cancer cell invasion. The aim of this study was to investigate the role of protein kinase C alpha (PKCα) played in amoeboid mode of cancer cell invasion. We showed that higher expression of PKCα resulted in mesenchymal-amoeboid transition of K2 and MDA mesenchymal cancer cell lines, which was accompanied with decreased cancer cell invasive capability in 3D collage matrix. PKCα overexpression had no effect on the cell morphology of A375m2, however, the results showed a trend in increased invasive potential of A375m2 cells. Conversely, the expression of dominant-negative PKCα resulted in amoeboid-mesenchymal transition of A375m2 cells, and it was associated with decreased invasive potential of K2 and MDA cell lines. Furthermore, a linkage between PKCα and phosphatidylinositol 3-kinase (PI3K) was tested. The results revealed that increased activity of PKCα was accompanied with decreased level of active Akt in K2 cell line. To summarize, our results suggest a probable role of PKCα in regulation of amoeboid...
|
|
|
Drug repurposing for the inhibition of invasiveness and metastasis of cancer cells
Turchyna, Kateryna ; Brábek, Jan (advisor) ; Jakubek, Milan (referee)
Metastasis is the primary cause of death from cancer. Current lack of medicines for metastasis makes it a topical issue and encourages the global search for molecules that may potentially inhibit invasiveness of cancer cells, and thus prevent metastatic spread. Drug repurposing is a strategy of identifying new uses for approved drugs that are outside the scope of the original medical indication. The aim of this thesis is to summarize knowledge on the repurposing potential of selected groups of drugs with emphasis on molecular mechanisms of their action. In particular, the work is focused on selected antipsychotics, antidepressants, beta- blockers and statins, whose abilities to inhibit cancer invasiveness have been indicated.
|
|
|
The role of protein kinase C alpha in individual cancer cell invasiveness
Szabadosová, Emília ; Brábek, Jan (advisor) ; Hlaváčková, Markéta (referee)
Protein kinase C alpha was one of the first identified isoenzyme of PKC family. Since then PKC has been shown to be important in various signal cascades. One of the best known role is in tumor invasiveness and in development of metastases. A role of protein kinase C alpha was pointed out in regulation of Rho/ROCK pathway in amoeboid invasiveness and also Raf/MAPK signaling cascade of mesenchymal movement. ERM proteins, which act in cancer invasiveness, are regulated by protein kinase C too.
|
|
|
Analysis of PKCα Influence on Cancer Cell Invasion.
Szabadosová, Emília ; Brábek, Jan (advisor) ; Nováková, Olga (referee)
7 Abstract Protein kinase C alpha (PKCα) is a serine/threonine protein kinase. PKCα is an important protein regulating cell polarity, protein secretion, apoptosis, cell proliferation and differentiation and tumorogenesis. Previous research has shown a role of PKCα also in a cancer cell migration and cancer cell invasion. The aim of this study was to investigate the role of protein kinase C alpha (PKCα) played in amoeboid mode of cancer cell invasion. We showed that higher expression of PKCα resulted in mesenchymal-amoeboid transition of K2 and MDA mesenchymal cancer cell lines, which was accompanied with decreased cancer cell invasive capability in 3D collage matrix. PKCα overexpression had no effect on the cell morphology of A375m2, however, the results showed a trend in increased invasive potential of A375m2 cells. Conversely, the expression of dominant-negative PKCα resulted in amoeboid-mesenchymal transition of A375m2 cells, and it was associated with decreased invasive potential of K2 and MDA cell lines. Furthermore, a linkage between PKCα and phosphatidylinositol 3-kinase (PI3K) was tested. The results revealed that increased activity of PKCα was accompanied with decreased level of active Akt in K2 cell line. To summarize, our results suggest a probable role of PKCα in regulation of amoeboid...
|
|
|
The role of protein kinase C alpha in individual cancer cell invasiveness
Szabadosová, Emília ; Brábek, Jan (advisor) ; Hlaváčková, Markéta (referee)
Protein kinase C alpha was one of the first identified isoenzyme of PKC family. Since then PKC has been shown to be important in various signal cascades. One of the best known role is in tumor invasiveness and in development of metastases. A role of protein kinase C alpha was pointed out in regulation of Rho/ROCK pathway in amoeboid invasiveness and also Raf/MAPK signaling cascade of mesenchymal movement. ERM proteins, which act in cancer invasiveness, are regulated by protein kinase C too.
|
guest ::
