Cho+kwang+Hyun
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A mechanism for how reactive oxygen species cause cell responses studied
A research team led by Professor Kwang-Hyun Cho of the Department of Biology and Brain Engineering, KAIST, and Dr. Gi-Sun Kwon of the Korea Research Institute of Bioscience and Biotechnology succeeded in proving the mechanism behind the determination of cell life in relation to reactive oxygen species.
The results of the venture were published in the June 3rd edition of Science Signaling. The title of the research paper is “MLK3 is part of a feedback mechanism that regulates different cellular responses to reactive oxygen species.”
The research team discovered that the molecular switch that determines the division of apoptosis of a cell was based on MLK3 feedback mechanism. MLK stands for mixed-lineage kinase.
Under sufficient stress, the mechanism instructs the cell to undergo the division but in an overly stressful environment, the mechanism stops the cell division and instead, induces apoptosis. This discovery is expected to be a breakthrough in illnesses related to the concentration of the reactive oxygen species (ROS).
At low concentration of ROS, the protein associated with cell division, ERK (extracellular-signal-regulated kinase), is activated while as the ROS concentration increases, JNK (c-Jun N-terminal protein kinases), responsible for apoptosis, becomes activated. Furthermore, through computer simulation analysis and mathematical modeling, in tandem with molecular cell biology experiments, the MLK3 based feedback mechanism was the fundamental molecular switch that determines the balance between ERK and JNK, and ultimately the cell’s responses.
Professor Cho commented that “the contradicting cell responses to ROS had remained a mystery, but with the system biology, an approach in which information technology and biotechnology converge, such riddles can be resolved. We expect that the proven mechanism will be used to overcome aging or cancer growth as a result of ROS in the near future.”
Picture shows the process of identifying cell responses caused by reactive oxygen species.
2014.06.13 View 8824 -
Systems biology demystifies the resistance mechanism of targeted cancer medication
Korean researchers have found the fundamental resistance mechanism of the MEK inhibitor, a recently highlighted chemotherapy method, laying the foundation for future research on overcoming cancer drug resistance and improving cancer survival rates. This research is meaningful because it was conducted through systems biology, a fusion of IT and biotechnology.
The research was conducted by Professor Gwang hyun Cho’s team from the Department of Biology at KAIST and was supported by the Ministry of Education, Science and Technology and the National Research Foundation of Korea.
The research was published as the cover paper for the June edition of the Journal of Molecular Cell Biology (Title: The cross regulation between ERK and PI3K signaling pathways determines the tumoricidal efficacy of MEK inhibitor).
Targeted anticancer medication targets certain molecules in the signaling pathway of the tumor cell and not only has fewer side effects than pre-existing anticancer medication, but also has high clinical efficacy. The technology also allows the creation of personalized medication and has been widely praised by scientists worldwide.
However, resistances to the targeted medication have often been found before or during the clinical stage, eventually causing the medications to fail to reach the drug development stage. Moreover, even if the drug is effective, the survival rate is low and the redevelopment rate is high.
An active pathway in most tumor cells is the ERK (Extracellular signal-regulated kinases) signaling pathway. This pathway is especially important in the development of skin cancer or thyroid cancer, which are developed by the mutation of the BRAF gene inside the path. In these cases, the MEK (Extracellular signal-regulated kinases) inhibitor is an effective treatment because it targets the pathway itself. However, the built-up resistance to the inhibitor commonly leads to the redevelopment of cancer.
Professor Cho’s research team used large scale computer simulations to analyze the fundamental resistance mechanism of the MEK inhibitor and used molecular cell biological experiments as well as bio-imaging* techniques to verify the results.
* Bio-imaging: Checking biological phenomena at the cellular and molecular levels using imagery
The research team used different mutational variables, which revealed that the use of the MEK inhibitor reduced the transmission of the ERK signal but led to the activation of another signaling pathway (the PI3K signaling pathway), reducing the effectiveness of the medication. Professor Cho’s team also found that this response originated from the complex interaction between the signaling matter as well as the feedback network structure, suggesting that the mix of the MEK inhibitor with other drugs could improve the effects of the targeted anticancer medication.
Professor Cho stated that this research was the first of its kind to examine the drug resistivity against the MEK inhibitor at the systematic dimension and showed how the effects of drugs on the signaling pathways of cells could be predicted using computer simulation. It also showed how basic research on signaling networks can be applied to clinical drug use, successfully suggesting a new research platform on overcoming resistance to targeting medication using its fundamental mechanism.
2012.07.06 View 10553