Research aim is the role of iron in the biology of TICs. Iron is an indispensible micro-nutrient which is critical for cellular metabolism, DNA synthesis and cellular respiration. Iron is usually incorporated into proteins as a metal cofactor resulting in the gain of catalytic function as evidenced in haemoglobin as a prime example.
Iron deprivation results in anemia and hypoxia and depriving cancer cells of iron via iron chelation or by blocking iron uptake results in apoptosis induction and demonstrates the fact that cancerous cells usually show higher demand for iron. Importantly, the iron metabolism of TICs has not been studied so far and our preliminary data show significant alterations in the iron metabolism in these cells. Our main goal is to define the changes in the iron metabolism in TICs on molecular level and show physiological importance of these findings and potentially utilize such knowledge for therapies that would target specifically TICs.
- Iron metabolism
- ABC transporter proteins
- Tumour-initiating cells
- Mitochondrial biology
- Characterize the alterations in iron metabolism between normal and tumour cells, specifically tumour-initiating cells
- Define the differences in the expression and regulation of ABC transporter in the tumour-initiating cells
- Identify of micro RNA that regulates mitochondrial function in normal and cancer cells
CONTENT OF THE RESEARCH:
The main aim of our research is to describe and identify novel targets of cancer cells, especially of tumour-initiating cells, which could be utilized to remove, reprogramm or specifically induce apoptosis in these cells. Our research is thus focusing on the biology of tumour-initiating cells and also the function and biology of mitochondria, including the utilization of mitochondria as targets for cancer therapy.
We have participed in pivotal studies that clearly document that mitochondrial targeting of vitamin E analogues significantly enhances its anti-tumour properties that are based on its unique properties to inhibit mitochondrial transcription, block angiogenesis and also induce apoptosis at higher doses.
We are also focusing on iron metabolism in the biology of tumour-initiating cells. Iron metabolism of cancer cells has been well studied with an established link between higher iron demand in the proliferation cancer cells, where iron withdrawal induces apoptosis. Iron metabolism in tumour-initiating cells has not yet beendescribed and is thus one of our research topics.
The third topic is the expression and biological role of ABC transporter proteins in tumour-initiating cells. There are several ABC transporters that mediate multi drug resistance (MOR) where these proteins are able to export chemotherapeutic drugs out of the cells, leading to therapy failure. The latest research shows that these molecular pumps may not only export exogenous substrates, but export and transport endogenous substrates resulting in changes that modify the tumour microenvironment. This research aim is funded by the Kellner Family Foundation.
POTENTIAL FOR COOPERATION:
We cooperate with Griffith University, Australia (prof. Neužil), The University of Oviedo (prof Carlos Lopez Otin), The University of California San Diego (Dr. Xin Du), Institute of Chemistry (Jan Stursa, Lukas Werner), First medical Faculty, Charles University (Dr. Krijt), Faculty of Science, Charles University (Dr. Rosel). Ph.D. students are welcome to find a short stay in the laboratory with similar focus to broaden their expertise.