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Iron metabolism in cancer cells
Beranová, Lea Marie ; Truksa, Jaroslav (advisor) ; Čermák, Vladimír (referee)
1Abstract: Cancer is one of the major causes of death in the present world. As the research of this disease has progressed, the attention of some scientists has been focused on a metabolism of iron and how it can be used to fight these rapidly proliferating invasive cells and stop their spreading. This work should serve as a brief review of iron metabolic processes from the iron absorption from dietary resources and recycled cell iron, to its usage in heme- or Fe/S clusters-proteins and storage in a form of ferritin, while highlighting the points that differ in cancer cells. It also gives a modest overview on the regulatory pathways of iron uptake and use, and mentions iron metabolism disorders such as iron-depletion and overload. Simultaneously it is denoting possible differences that could be targeted in tumor treatment, and, at least but not last, the perspectives and future work that could bring a new methods and approaches to this matter. Keywords: iron metabolism, iron, cancer, hepcidin
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Role of sulfhydryl oxidase 1 in cancerogenesis
Beranová, Lea Marie ; Truksa, Jaroslav (advisor) ; Šuťák, Róbert (referee)
Disulfide bridges play a significant role in protein-folding as well as en- zyme activity and thus regulate many intra- and extracellular processes. Sulfhydryl oxidase QSOX1 forms S-S bridges de novo, modulating the activity of its substrates and thus directly or indirectly influences vital cel- lular processes. The first part of this thesis focuses on characterization of the role of QSOX1 in cancerogenesis, using breast cancer cell lines (MCF7, MDA-MB-231) and pancreatic cancer cell line (Panc-1), while the second part emphasizes the regulation of QSOX1 expression by different oxygen concentrations. To study the effect of QSOX1 on proliferation of triple-negative cancer cells MDA-MB-231, two genetically modified cell lines - QSOX1-overexpressing and QSOX1 knockout cell lines - were constructed. While increased QSOX1 protein levels do not have a significant effect, the absence of QSOX1 leads to a decreased cellular growth. Lack of QSOX1 also results in visible change in cellular morphology. QSOX1 knockout cells can be mostly characterized as more round-shaped with less noticeable or completely missing lamellipo- dia. This finding is with agreement with to-date literature suggesting that QSOX1 is important not only for cellular proliferation but also for migration and invasiveness. While authenticating the theory of...
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Role of sulfhydryl oxidase 1 in cancerogenesis
Beranová, Lea Marie ; Truksa, Jaroslav (advisor) ; Šuťák, Róbert (referee)
Disulfide bridges play a significant role in protein-folding as well as en- zyme activity and thus regulate many intra- and extracellular processes. Sulfhydryl oxidase QSOX1 forms S-S bridges de novo, modulating the activity of its substrates and thus directly or indirectly influences vital cel- lular processes. The first part of this thesis focuses on characterization of the role of QSOX1 in cancerogenesis, using breast cancer cell lines (MCF7, MDA-MB-231) and pancreatic cancer cell line (Panc-1), while the second part emphasizes the regulation of QSOX1 expression by different oxygen concentrations. To study the effect of QSOX1 on proliferation of triple-negative cancer cells MDA-MB-231, two genetically modified cell lines - QSOX1-overexpressing and QSOX1 knockout cell lines - were constructed. While increased QSOX1 protein levels do not have a significant effect, the absence of QSOX1 leads to a decreased cellular growth. Lack of QSOX1 also results in visible change in cellular morphology. QSOX1 knockout cells can be mostly characterized as more round-shaped with less noticeable or completely missing lamellipo- dia. This finding is with agreement with to-date literature suggesting that QSOX1 is important not only for cellular proliferation but also for migration and invasiveness. While authenticating the theory of...
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Iron metabolism in cancer cells
Beranová, Lea Marie ; Truksa, Jaroslav (advisor) ; Čermák, Vladimír (referee)
1Abstract: Cancer is one of the major causes of death in the present world. As the research of this disease has progressed, the attention of some scientists has been focused on a metabolism of iron and how it can be used to fight these rapidly proliferating invasive cells and stop their spreading. This work should serve as a brief review of iron metabolic processes from the iron absorption from dietary resources and recycled cell iron, to its usage in heme- or Fe/S clusters-proteins and storage in a form of ferritin, while highlighting the points that differ in cancer cells. It also gives a modest overview on the regulatory pathways of iron uptake and use, and mentions iron metabolism disorders such as iron-depletion and overload. Simultaneously it is denoting possible differences that could be targeted in tumor treatment, and, at least but not last, the perspectives and future work that could bring a new methods and approaches to this matter. Keywords: iron metabolism, iron, cancer, hepcidin
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