Publications by authors named "Jungsug Gwak"

A suture is a ubiquitous medical device to hold wounded tissues together and support the healing process after surgery. Surgical sutures, having incomplete biocompatibility, often cause unwanted infections or serious secondary trauma to soft or fragile tissue. In this research, UV/ozone (UVO) irradiation or polystyrene sulfonate acid (PSS) dip-coating is used to achieve a fibronectin (FN)-coated absorbable suture system, in which the negatively charged moieties produced on the suture cause fibronectin to change from a soluble plasma form into a fibrous form, mimicking the actions of cellular fibronectin upon binding.

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Article Synopsis
  • Infiltration of preadipocytes and tumor-associated macrophages (TAMs) into the prostate tumor microenvironment is influenced by the regulation of SFMBT2, which impacts cancer progression.
  • Down-regulation of SFMBT2 results in increased levels of specific proteins (CXCL8, CCL2, CXCL10, and CCL20) that promote the infiltration of these cells, particularly in patients with higher Gleason scores.
  • SFMBT2's regulatory role suggests it may be a promising target for therapy to reduce prostate cancer metastasis and could serve as a potential biomarker for the disease.
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It has been suggested that Jmjd6 plays an important role in gene regulation through its demethylation or hydroxylation activity on histone and transcription factors. In addition, Jmjd6 has been shown to regulate RNA splicing by interaction with splicing factors. In this study, we demonstrated that Jmjd6a is expressed in developing Xenopus laevis eye during optic vesicle formation and retinal layer differentiation stages.

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The tumor suppressor p53 plays essential roles in cellular protection mechanisms against a variety of stress stimuli and its activation induces apoptosis or autophagy in certain cancer cells. Here, we identified protopine, an isoquinoline alkaloid isolated from Nandina domestica, as an activator of the p53 pathway from cell-based natural compound screening based on p53-responsive transcription. Protopine increased the p53-mediated transcriptional activity and promoted p53 phosphorylation at the Ser15 residue, resulting in stabilization of p53 protein.

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Axin1, a concentration-limiting component of the β-catenin destruction complex, negatively regulates the Wnt/β-catenin pathway. Axin1 concentration is reported to be regulated by proteasomal degradation; however, its transcriptional regulation has not yet been reported. Here, we demonstrated that CCAAT/enhancer-binding protein-β (C/EBP-β) activates axis inhibition protein 1 (AXIN1) gene expression, thereby attenuating Wnt/β-catenin signaling.

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Aberrant up-regulation of Wnt/β-catenin signaling is associated with the development and progression of prostate cancer, but the underlying mechanism is unclear. Here we show that in the absence of androgens, the Wnt/β-catenin pathway activates AR-mediated transcription through up-regulation of the Hippo pathway effector Yes-associated protein (YAP). Wnt3a-conditioned medium (Wnt3a-CM) promotes the growth of LNCaP cells and increases AR and YAP protein levels.

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Metastatic prostate cancer is the leading cause of morbidity and mortality in men. In this study, we found that expression level of SFMBT2 is altered during prostate cancer progression and has been associated with the migration and invasion of prostate cancer cells. The expression level of SFMBT2 is high in poorly metastatic prostate cancer cells compared to highly metastatic prostate cancer cells.

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Human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is the primary determinant for telomerase enzyme activity, which has been associated with cellular immortality. Expression of the hTERT gene is regulated by various extracellular (external) stimuli and is aberrantly up-regulated in more than 90% of cancers. Here we show that hTERT gene expression was repressed in response to transforming growth factor-β (TGF-β) by a mechanism dependent on transcription factors Snail and c-Myc.

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(-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been reported to inhibit the Wnt/β-catenin pathway, which is aberrantly up-regulated in colorectal cancers, but its precise mechanism of action remains unclear. Here, we used a sensitive cell-based system to demonstrate that EGCG suppresses β-catenin response transcription (CRT), activated by Wnt3a-conditioned medium (Wnt3a-CM), by promoting the degradation of intracellular β-catenin. EGCG induced β-catenin N-terminal phosphorylation at the Ser33/37 residues and subsequently promoted its degradation; however, this effect was not observed for oncogenic forms of β-catenin.

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Protein kinase Cα (PKCα) phosphorylates the Ser33/37/Thr41 residues of β-catenin, which lacks a typical PKCα canonical sequence, but little is known about its underlying mechanism. Here we showed that Ser33/Ser37/Thr41 of β-catenin fragments encompassing the armadillo repeats 1-5 (β-catenin1-781, β-catenin1-682, and β-catenin1-422) are phosphorylated by PKCα whereas β-catenin1-138 lacking these repeats is not phosphorylated. Binding-site analysis revealed that PKCα directly interacts with β-catenin through the sites on the armadillo repeats 1-5.

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Aberrant accumulation of intracellular β-catenin and subsequent activation of β-catenin response transcription (CRT) in intestinal epithelial cells is a frequent early event during the development of colon cancer. Here we show that cardamonin, a chalcone isolated from Aplinia katsumadai Hayata, inhibited CRT in SW480 colon cancer cells that carry inactivating mutation in the adenomatous polyposis coli (APC) gene. Cardamonin also down-regulated intracellular β-catenin levels in SW480 cells without affecting its mRNA levels.

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Aberrant accumulation of intracellular β-catenin is a well recognized characteristic of several cancers, including prostate, colon, and liver cancers, and is a potential target for development of anticancer therapeutics. Here, we used cell-based small molecule screening to identify CGK062 as an inhibitor of Wnt/β-catenin signaling. CGK062 promoted protein kinase Cα (PKCα)-mediated phosphorylation of β-catenin at Ser33/Ser37, marking it for proteasomal degradation.

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The Wnt/β-catenin pathway plays important roles in the differentiation of multiple cell types, including mesenchymal stem cells. Using a cell-based chemical screening assay with a synthetic chemical library of 270 000 compounds, we identified the compound SKL2001 as a novel agonist of the Wnt/β-catenin pathway and uncovered its molecular mechanism of action. SKL2001 upregulated β-catenin responsive transcription by increasing the intracellular β-catenin protein level and inhibited the phosphorylation of β-catenin at residues Ser33/37/Thr41 and Ser45, which would mark it for proteasomal degradation, without affecting CK1 and GSK-3β enzyme activities.

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The tumor suppressor p53 plays an important role in cellular emergency mechanisms through regulating the genes involved in cell cycle arrest and apoptosis. To identify small molecules that can activate p53-responsive transcription, we performed chemical screening using genetically engineered HCT116 reporter cells. We found that TopIn (7-phenyl-6H-[1,2,5]oxadiazolo[3,4-e]indole 3-oxide) efficiently activated p53-mediated transcriptional activity and induced phosphorylation of p53 at Ser15, thereby stabilizing the p53 protein.

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Galangin is a naturally occurring bioflavonoid with anticancer activity against certain human cancers, yet little is known about its mechanism of action. Here, we used a chemical biology approach to reveal that galangin suppresses β-catenin response transcription (CRT), which is aberrantly up-regulated in colorectal and liver cancers, by promoting the degradation of intracellular β-catenin. Inhibition of glycogen synthase kinase-3β (GSK-3β) activity or mutation of the GSK-3β-targeted sequence from β-catenin was unable to abrogate the galangin-mediated degradation of β-catenin.

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Cdc25A phosphatase, which is essential in cell cycle progression, is degraded by the proteasome throughout interphase and in response to genotoxic stress. Phosphorylation of Cdc25A on Ser82 in the DSG motif is important in the recognition by β-TrCP, resulting in targeting of Cdc25A for ubiquitination. Chk1 is known to phosphorylate Cdc25A on Ser76, and NEK11 or CK1α relays phosphorylation of Cdc25A to Ser82 in a hierarchical manner.

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Abnormal regulation of Wnt/beta-catenin signaling followed by increased levels of the beta-catenin protein have been identified in enhanced cellular proliferation and development of colon polyps and cancers. To inhibit beta-catenin gene expression in colon cancer cells, RNA-cleaving oligodeoxyribozyme (DNAzyme) was employed to destroy the beta-catenin mRNA. We designed a strategy to identify the cleavage sites in beta-catenin RNA with a pool of random sequences from a DNAzyme library and identified four potential DNAzyme-working sites.

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We reported previously that protein kinase C-alpha (PKC-alpha) negatively regulates Wnt/beta-catenin signalling pathway. The current study explores the role of PKC-alpha in the regulation of proliferation of colon cancer cells, which contain aberrant up-regulation of intracellular beta-catenin. In colon tissue and cells, an inverse correlation was observed between the expression levels of PKC-alpha and intracellular beta-catenin.

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Molecular lesions in Wnt/beta-catenin signaling and subsequent up-regulation of beta-catenin response transcription (CRT) occur frequently during the development of colon cancer. To identify small molecules that suppress CRT, we screened natural compounds in a cell-based assay for detection of TOPFalsh reporter activity. Murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa, antagonized CRT that was stimulated by Wnt3a-conditioned medium (Wnt3a-CM) or LiCl, an inhibitor of glycogen synthase kinase-3beta (GSK-3beta), and promoted the degradation of intracellular beta-catenin without altering its N-terminal phosphorylation at the Ser33/37 residues, marking it for proteasomal degradation, or the expression of Siah-1, an E3 ubiquitin ligase.

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Aberrant accumulation of intracellular beta-catenin in intestinal epithelial cells is a frequent early event during the development of colon cancer. To identify small molecules that decrease the level of intracellular beta-catenin, we performed cell-based chemical screening using genetically engineered HEK293 reporter cells to detect compounds that inhibit TOPFlash reporter activity, which was stimulated by Wnt3a-conditioned medium. We found that isoreserpine promoted the degradation of intracellular beta-catenin by up-regulation of Siah-1 in HEK293 and HCT116 colon cancer cells.

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The Wnt/beta-catenin signaling pathway plays important roles in cell differentiation. Activation of this pathway, likely by Wnt-10b, has been shown to inhibit adipogenesis in cultured 3T3-L1 preadipocytes and mice. Here we revealed that bisindoylmaleimide I (BIM), which is widely used as a specific inhibitor of protein kinase C (PKC), inhibits adipocyte differentiation through activation of the Wnt/beta-catenin signaling pathway.

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It is well known that CYP2C19 is an enzyme showing genetic polymorphism that may cause marked interindividual and interethnic variation in the metabolism and disposition of its substrates. This study compared the frequency distribution of CYP2C19*1, *2, and *3 alleles in Korean and Vietnamese populations, representing Far Eastern and Southwestern Asian populations, respectively. The presence of the CYP2C19 variant alleles was analyzed in 377 Korean and 165 Vietnamese healthy subjects using a new pyrosequencing method.

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Normally, the Wnt/beta-catenin pathway controls developmental processes and homeostasis, but abnormal activation of this pathway is a frequent event during the development of cancer. The key mechanism in regulation of the Wnt/beta-catenin pathway is the amino-terminal phosphorylation of beta-catenin, marking it for proteasomal degradation. Here we present small-molecule-based identification of protein kinase C (PKC)-mediated beta-catenin phosphorylation as a novel mechanism regulating the Wnt/beta-catenin pathway.

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Aberrant activation of Wnt/beta-catenin signaling and subsequent up-regulation of beta-catenin response transcription (CRT) is a critical event in the development of human colon cancer. Thus, Wnt/beta-catenin signaling is an attractive target for the development of anticancer therapeutics. In this study, we identified hexachlorophene as an inhibitor of Wnt/beta-catenin signaling from cell-based small-molecule screening.

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