TaeWoo Kwon

Pusan National University, Tsau-liang-hai, Busan, South Korea

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Publications (5)9.62 Total impact

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    ABSTRACT: PAK1 kinase has an essential role in tumorigenesis and cell survival in many cancers but its regulation is not fully understood. In this study, we showed that in response to irradiation of lung cancer cells, PAK1 was upregulated, tyrosine phosphorylated and translocated to the nucleus. Tyrosine phosphorylation relied upon JAK2 kinase activity and was essential for PAK1 protein stability and binding to Snail. This radiation-induced JAK2/PAK1/Snail signaling pathway increased epithelial-mesenchymal transition (EMT) by regulating epithelial and mesenchymal cell markers. Notably, JAK2 inhibitors mediated radiosensitization and EMT blockade in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that JAK2 phosphorylates and stabilizes functions of PAK1 that promote EMT and radioresistance in lung cancer cells, with additional implications for the use of JAK2 inhibitors as radiosensitizers in lung cancer treatment.
    Cancer research. 08/2014;
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    ABSTRACT: Radiotherapy plays a critical role in the treatment of non-small cell lung cancer (NSCLC). However, radioresistance is a major barrier against increasing the efficiency of radiotherapy for NSCLC. To understand the mechanisms underlying NSCLC radioresistance, we previously focused on the potential involvement of PIM1, PRAS40, FOXO3a, 14-3-3, and protein phosphatases. Among these proteins, PIM1 functioned as an oncogene and was found to act as a crucial mediator in radioresistant NSCLC cells. Therefore, we investigated the use of PIM1-specific inhibitors as novel therapeutic drugs to regulate radiosensitivity in NSCLC. After structure-based drug selection, SGI-1776, ETP-45299, and tryptanthrin were selected as candidates of PIM1 inhibitors that act as radiosensitizers. With irradiation, these drugs inhibited only PIM1 kinase activity without affecting PIM1 mRNA/protein levels or cellular localization. When PIM1 kinase activity was suppressed by these inhibitors, PRAS40 was not phosphorylated. Consequently, unphosphorylated PRAS40 did not form trimeric complexes with 14-3-3 and FOXO3a, leading to increased nuclear localization of FOXO3a. Nuclear FOXO3a promoted the expression of pro-apoptotic proteins such as Bim and FasL, resulting in a radiosensitizing effect on radioresistant NSCLC cells. Moreover, an in vivo xenograft mouse model confirmed this radiosensitizing effect induced by PIM1 inhibitors. In these model systems, tumor volume was significantly reduced by a combinational treatment with irradiation and PIM1 inhibitors compared to irradiation alone. Taken together, our findings provided evidence that PIM1-specific inhibitors, SGI-1776, ETP-45299, and tryptanthrin, can act as novel radiosensitizers to enhance the efficacy of radiotherapy by inhibiting irradiation-induced signaling pathway associated with radioresistance.
    Pharmacological Research 01/2013; · 4.35 Impact Factor
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    ABSTRACT: Several recent biological science studies have been focused on nanotechnology and nanomaterials due to their potential use in biomedicine. Drug delivery systems are an example of biomedical applications utilizing nanoparticles. Silver nanoparticles (AgNPs) can be used for these drug delivery systems. However, the effects of cytotoxicity caused by AgNPs are not fully understood. Determining the optimal characteristics to facilitate the biocompatibility of AgNPs is an important subject for application. In the present study, human erythrocytes were used as an in vitro model to examine the size, dose, and coating surfactant-dependent cytotoxicity of AgNPs. Our results demonstrated that polyvinylpyrrolidone (PVP) was a more suitable surfactant than polyethylene glycol (PEG) for AgNPs capping. In addition, we determined the appropriate particular size and dosage of AgNPs to reduce human erythrocytes hemolysis. Membrane damages including hemolysis, potassium efflux, protein leakage, and alterations in cell shape and membrane fragility were minimized with 100-nm AgNP particles. This study provides novel insights into AgNPs cytotoxicity and a basis for utilizing AgNPs for diagnostic and therapeutic applications.
    Journal of Nanoscience and Nanotechnology 08/2012; 12(8):6168-75. · 1.15 Impact Factor
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    ABSTRACT: Resistance of cancer cells to ionizing radiation plays an important role in the clinical setting of lung cancer treatment. To date, however, the exact molecular mechanism of radiosensitivity has not been well explained. In this study, we compared radioresistance in two types of non-small cell lung cancer (NSCLC) cells, NCI-H460 and A549, and investigated the signaling pathways that confer radioresistance. In radioresistant cells, exposure to radiation led to overexpression of PIM1 and reduction of protein phosphatases (PP2A and PP5), which induced translocation of PIM1 into the nucleus. Increased nuclear PIM1 phosphorylated PRAS40. Consequently, pPRAS40 made a trimeric complex with 14-3-3 and AKT-activated pFOXO3a, which then moved rapidly to the cytoplasm. Cytoplasmic retention of FOXO3a was associated with downregulation of proapoptotic genes and possibly radioresistance. On the other hand, no suppressive effect of radiation on protein phosphatases was detected and, concomitantly, protein phosphatases downregulated PIM1 in radiosensitive cells. In this setting, PIM1-activated pPRAS40, AKT-activated pFOXO3a, and their complex formation with 14-3-3 could be key regulators of the radiation-induced radioresistance in NSCLC cells.
    Radiation Research 09/2011; 176(5):539-52. · 2.70 Impact Factor
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    ABSTRACT: Cytochrome P450s (P450s) are the most versatile biological catalysts in plants; however, because the structure of the P450s has not been fully established, their broad substrate specificity has been limitedly discussed. p-coumarate-3-hydroxylase (C3H) is an essential enzyme for the biosynthesis of phenolic natural products in plants, but all attempts to express and purify C3H, have failed. In this research, we developed a bacterial expression of Arabidopsis C3H by combinational mutagenesis and purified C3H as a catalytically active form. The modified C3H could be purified in the absence of detergent, and crystallized in two forms (orthorhombic and trigonal space group) under different conditions. X-ray diffraction was processed to a 4.0 Å resolution (first type crystal) and a 3.8 Å resolution (second type crystal). Although the diffraction results of C3H(mod) crystals are not enough to determine crystallographic structure due to low resolution, the simplicity and rapidity of this technology are competitive advantages in comparison with other methods, and may contribute to structural analyses of other membrane proteins including P450s family.
    Protein Expression and Purification 04/2011; 79(1):149-55. · 1.43 Impact Factor