Hyun Seung Yoo

The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e.g. genomics, transcriptomics, protein-protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10,000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issue.

Funded by the National Institute of Allergy and Infectious Diseases, the Pathosystems Resource Integration Center (PATRIC) is a genomics-centric relational database and bioinformatics resource designed to assist scientists in infectious-disease research. Specifically, PATRIC provides scientists with (i) a comprehensive bacterial genomics database, (ii) a plethora of associated data relevant to genomic analysis, and (iii) an extensive suite of computational tools and platforms for bioinformatics analysis. While the primary aim of PATRIC is to advance the knowledge underlying the biology of human pathogens, all publicly available genome-scale data for bacteria are compiled and continually updated, thereby enabling comparative analyses to reveal the basis for differences between infectious free-living and commensal species. Herein we summarize the major features available at PATRIC, dividing the resources into two major categories: (i) organisms, genomes, and comparative genomics and (ii) recurrent integration of community-derived associated data. Additionally, we present two experimental designs typical of bacterial genomics research and report on the execution of both projects using only PATRIC data and tools. These applications encompass a broad range of the data and analysis tools available, illustrating practical uses of PATRIC for the biologist. Finally, a summary of PATRIC's outreach activities, collaborative endeavors, and future research directions is provided.

MOTIVATION: We've developed a highly curated bacterial virulence factor (VF) library in PATRIC (Pathosystems Resource Integration Center, www.patricbrc.org) to support infectious disease research. Although several VF databases are available, there is still a need to incorporate new knowledge found in published experimental evidence and integrate these data with other information known for these specific VF genes, including genomic and other omics data. This integration supports the identification of VFs, comparative studies and hypothesis generation, which facilitates the understanding of virulence and pathogenicity. RESULTS: We have manually curated VFs from six prioritized NIAID (National Institute of Allergy and Infectious Diseases) category A-C bacterial pathogen genera, Mycobacterium, Salmonella, Escherichia, Shigella, Listeria and Bartonella, using published literature. This curated information on virulence has been integrated with data from genomic functional annotations, trancriptomic experiments, protein-protein interactions and disease information already present in PATRIC. Such integration gives researchers access to a broad array of information about these individual genes, and also to a suite of tools to perform comparative genomic and transcriptomics analysis that are available at PATRIC. AVAILABILITY AND IMPLEMENTATION: All tools and data are freely available at PATRIC (http://patricbrc.org). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Syndecan-2, a transmembrane heparan sulfate proteoglycan, is a critical mediator in the tumorigenesis of colon carcinoma cells. We explored the function of syndecan-2 in melanoma, one of the most invasive types of cancers, and found that the expression of this protein was elevated in tissue samples from both nevus and malignant human melanomas but not in melanocytes of the normal human skin tissues. Similarly, elevated syndecan-2 expression was observed in various melanoma cell lines. Overexpression of syndecan-2 enhanced migration and invasion of melanoma cells, whereas the opposite was observed when syndecan-2 levels were knocked down using small inhibitory RNAs. Syndecan-2 expression was enhanced by fibroblast growth factor-2, which is known to stimulate melanoma cell migration; however, α-melanocyte-stimulating hormone decreased syndecan-2 expression and melanoma cell migration and invasion in a melanin synthesis-independent manner. Furthermore, syndecan-2 overexpression rescued the migration defects induced by α-melanocyte-stimulating hormone treatment. Together, these data strongly suggest that syndecan-2 plays a crucial role in the migratory potential of melanoma cells. Syndecan-2, a transmembrane heparan sulfate proteoglycan, is a critical mediator in the tumorigenesis of colon carcinoma cells. We explored the function of syndecan-2 in melanoma, one of the most invasive types of cancers, and found that the expression of this protein was elevated in tissue samples from both nevus and malignant human melanomas but not in melanocytes of the normal human skin tissues. Similarly, elevated syndecan-2 expression was observed in various melanoma cell lines. Overexpression of syndecan-2 enhanced migration and invasion of melanoma cells, whereas the opposite was observed when syndecan-2 levels were knocked down using small inhibitory RNAs. Syndecan-2 expression was enhanced by fibroblast growth factor-2, which is known to stimulate melanoma cell migration; however, α-melanocyte-stimulating hormone decreased syndecan-2 expression and melanoma cell migration and invasion in a melanin synthesis-independent manner. Furthermore, syndecan-2 overexpression rescued the migration defects induced by α-melanocyte-stimulating hormone treatment. Together, these data strongly suggest that syndecan-2 plays a crucial role in the migratory potential of melanoma cells. The syndecans, a family of four transmembrane cell surface heparan sulfate proteoglycans, mainly serving as a co-receptor, regulate the adhesion-dependent signal transduction of a variety of cell types, including cancer cells (1Bass M.D. Humphries M.J. Biochem. J. 2002; 368: 1-15Crossref PubMed Scopus (118) Google Scholar, 2Sebestyén A. Tótth A. Mihalik R. Szakács O. Paku S. Kopper L. Tumour Biol. 2000; 21: 349-357Crossref PubMed Scopus (12) Google Scholar). Cell adhesion receptors or co-receptors play a critical role in the neoplastic transformation of normal cells by regulating the induction of cancer-specific cellular behavior and morphology. Thus, cancer cells probably express and utilize a distinct set of syndecans in the regulation of cancer cell growth. Several reports have linked altered syndecan expression to various elements of cancer cell growth. Loss of syndecan-1 correlates with shorter survival times in patients with squamous cell carcinoma of the head, neck, and lung (3Park H. Kim Y. Lim Y. Han I. Oh E.S. J. Biol. Chem. 2002; 277: 29730-29736Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar) as well as multiple myeloma (4Purushothaman A. Chen L. Yang Y. Sanderson R.D. J. Biol. Chem. 2008; 283: 32628-32636Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar); loss of syndecan-1 is also associated with an elevated potential for metastasis in patients with hepatocellular and colorectal carcinomas (5Contreras H.R. Fabre M. Granés F. Casaroli-Marano R. Rocamora N. Herreros A.G. Reina M. Vilaró S. Biochem. Biophys. Res. Commun. 2001; 286: 742-751Crossref PubMed Scopus (40) Google Scholar, 6Munesue S. Kusano Y. Oguri K. Itano N. Yoshitomi Y. Nakanishi H. Yamashina I. Okayama M. Biochem. J. 2002; 363: 201-209Crossref PubMed Scopus (61) Google Scholar). Previous studies have shown that syndecan-1 regulates tumor activity in pancreatic (7Beauvais D.M. Rapraeger A.C. Reprod. Biol. Endocrinol. 2004; 2: 3Crossref PubMed Scopus (209) Google Scholar), gastric (8Kim Y. Park H. Lim Y. Han I. Kwon H.J. Woods A. Oh E.S. Oncogene. 2003; 22: 826-830Crossref PubMed Scopus (33) Google Scholar), and breast carcinomas (9Modrowski D. Baslé M. Lomri A. Marie P.J. J. Biol. Chem. 2000; 275: 9178-9185Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar). Syndecan-1 may thus play multiple roles in tumorigenic activity and perform various tissue- and/or tumor stage-specific functions (10Kusano Y. Oguri K. Nagayasu Y. Munesue S. Ishihara M. Saiki I. Yonekura H. Yamamoto H. Okayama M. Exp. Cell Res. 2000; 256: 434-444Crossref PubMed Scopus (86) Google Scholar). Syndecan-4 expression is reduced in colon carcinoma cells (11Wang H.B. Dembo M. Hanks S.K. Wang Y. Proc. Natl. Acad. Sci. U.S.A. 2001; 98: 11295-11300Crossref PubMed Scopus (388) Google Scholar, 12Guan J.L. Matrix Biol. 1997; 16: 195-200Crossref PubMed Scopus (130) Google Scholar) and appears to correlate with increased tumorigenic activity (e.g. cell migration and invasion (13Hauck C.R. Sieg D.J. Hsia D.A. Loftus J.C. Gaarde W.A. Monia B.P. Schlaepfer D.D. Cancer Res. 2001; 61: 7079-7090PubMed Google Scholar)), implying that syndecan-4 functions as a tumor suppressor. Syndecan-2 is also known to play a crucial role in the regulation of cancer activity. Increased levels of syndecan-2 confer an invasive phenotype in lung (14Nackaerts K. Verbeken E. Deneffe G. Vanderschueren B. Demedts M. David G. Int. J. Cancer. 1997; 74: 335-345Crossref PubMed Scopus (114) Google Scholar) and colon cancer cells (15Agochiya M. Brunton V.G. Owens D.W. Parkinson E.K. Paraskeva C. Keith W.N. Frame M.C. Oncogene. 1999; 18: 5646-5653Crossref PubMed Scopus (208) Google Scholar). Reduction in syndecan-2 expression induces cells to switch from the transformed phenotype to flattened monolayers (8Kim Y. Park H. Lim Y. Han I. Kwon H.J. Woods A. Oh E.S. Oncogene. 2003; 22: 826-830Crossref PubMed Scopus (33) Google Scholar) and reduces tumorigenic activity in colon adenocarcinoma and fibrosarcoma cells (8Kim Y. Park H. Lim Y. Han I. Kwon H.J. Woods A. Oh E.S. Oncogene. 2003; 22: 826-830Crossref PubMed Scopus (33) Google Scholar, 16Jayson G.C. Vives C. Paraskeva C. Schofield K. Coutts J. Fleetwood A. Gallagher J.T. Int. J. Cancer. 1999; 82: 298-304Crossref PubMed Scopus (48) Google Scholar). In addition, syndecan-2 is highly expressed in the microvasculature of mouse gliomas and has been shown to regulate angiogenesis in microvascular endothelial cells (17Fears C.Y. Gladson C.L. Woods A. J. Biol. Chem. 2006; 281: 14533-14536Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar). On the other hand, an inverse correlation between syndecan-2 expression and metastatic potential has been found in Lewis lung carcinoma cell lines (6Munesue S. Kusano Y. Oguri K. Itano N. Yoshitomi Y. Nakanishi H. Yamashina I. Okayama M. Biochem. J. 2002; 363: 201-209Crossref PubMed Scopus (61) Google Scholar). Therefore, changes in syndecan-2 expression may directly or indirectly regulate cancer growth. Melanoma is the most aggressive malignant tumor of melanocytes. Although found predominantly in the skin, primary melanomas are also known to occur in the bowel and eye (18Markovic S.N. Erickson L.A. Rao R.D. Weenig R.H. Pockaj B.A. Bardia A. Vachon C.M. Schild S.E. McWilliams R.R. Hand J.L. Laman S.D. Kottschade L.A. Maples W.J. Pittelkow M.R. Pulido J.S. Cameron J.D. Creagan E.T. Mayo Clin. Proc. 2007; 82: 364-380Abstract Full Text Full Text PDF PubMed Scopus (363) Google Scholar). Malignant melanoma is notoriously one of the most difficult cancers to treat (19Hocker T.L. Singh M.K. Tsao H. J. Invest. Dermatol. 2008; 128: 2575-2595Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar). Therefore, identifying and understanding molecules that regulate the aggressive melanoma phenotype is essential for predicting the likelihood of metastasis. Interestingly, previous studies have shown that melanoma cells acquire the ability to recognize components of the extracellular matrix (ECM) 2The abbreviations used are: ECMextracellular matrixMSHmelanocyte-stimulating hormone(s)FGFfibroblast growth factorDMEMDulbecco's modified Eagle's mediumFAKfocal adhesion kinaseFBSfetal bovine serumPBSphosphate-buffered salinemAbmonoclonal antibodyBPEbovine pituitary extractsiRNAsmall interfering RNA. 2The abbreviations used are: ECMextracellular matrixMSHmelanocyte-stimulating hormone(s)FGFfibroblast growth factorDMEMDulbecco's modified Eagle's mediumFAKfocal adhesion kinaseFBSfetal bovine serumPBSphosphate-buffered salinemAbmonoclonal antibodyBPEbovine pituitary extractsiRNAsmall interfering RNA. via the ectopic expression of different ECM receptors during invasion of the basement membrane (20Hess A.R. Postovit L.M. Margaryan N.V. Seftor E.A. Schneider G.B. Seftor R.E. Nickoloff B.J. Hendrix M.J. Cancer Res. 2005; 65: 9851-9860Crossref PubMed Scopus (125) Google Scholar). Indeed, invadopodia, the dynamic organelle-like structures that form actin-rich protrusions with ECM proteolytic activity, adhere to and digest collagens, laminins, and fibronectin (21Stylli S.S. Kaye A.H. Lock P. J. Clin. Neurosci. 2008; 15: 725-737Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar). The adhesive properties of invadopodia are primarily attributed to integrins, a large family of heterodimeric transmembrane receptors composed of α and β subunits (22Linder S. Aepfelbacher M. Trends Cell Biol. 2003; 13: 376-385Abstract Full Text Full Text PDF PubMed Scopus (503) Google Scholar). For example, β1 integrins localize within the invadopodia of melanoma cells (23Nakahara H. Nomizu M. Akiyama S.K. Yamada Y. Yeh Y. Chen W.T. J. Biol. Chem. 1996; 271: 27221-27224Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar), and the α5β1 integrins are enriched peripherally in invadopodia, where they stabilize invadopodia protrusion (24Mueller S.C. Ghersi G. Akiyama S.K. Sang Q.X. Howard L. Pineiro-Sanchez M. Nakahara H. Yeh Y. Chen W.T. J. Biol. Chem. 1999; 274: 24947-24952Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar). Ectopic stimulation of α6β1 integrin with laminin peptides or with β1 or α6 integrin stimulatory antibodies increases invadopodia activity and melanoma invasiveness (23Nakahara H. Nomizu M. Akiyama S.K. Yamada Y. Yeh Y. Chen W.T. J. Biol. Chem. 1996; 271: 27221-27224Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar). The invasive behavior of melanoma cells can be attributed to increased cell motility caused by changes in cytoskeletal organization and altered contacts with the ECM. Thus, cell adhesion receptors may play a crucial role in the acquisition of highly migratory behavior. extracellular matrix melanocyte-stimulating hormone(s) fibroblast growth factor Dulbecco's modified Eagle's medium focal adhesion kinase fetal bovine serum phosphate-buffered saline monoclonal antibody bovine pituitary extract small interfering RNA. extracellular matrix melanocyte-stimulating hormone(s) fibroblast growth factor Dulbecco's modified Eagle's medium focal adhesion kinase fetal bovine serum phosphate-buffered saline monoclonal antibody bovine pituitary extract small interfering RNA. Syndecan-2 acts as a key regulator of cancer cells, suggesting that syndecan-2 may contribute to the aggressive phenotype and metastatic potential of melanoma. Here, we report that syndecan-2 plays a pivotal role in the migratory activity of melanoma cells. Monoclonal antibodies (mAbs) to vinculin, paxillin, and phosphotyrosine (4G10) were purchased from Upstate Biotechnology, Inc. (Lake Placid, NY). mAb to focal adhesion kinase (FAK) and polyclonal antibodies to phosphorylation site-specific FAK(Tyr(P)397) and FAK(Tyr(P)861) were purchased from BioSource Quality Controlled Biochemicals, Inc. (Morgan Hill, CA). Monoclonal antibody to human melanosome (clone HMB-45) was purchased from Dako (Denmark). Effectene was from Qiagen (Hilden, Germany), bovine pituitary extract (BPE) was from Lonza (Visp, Switzerland), α-melanocyte-stimulating hormone (MSH) was from Sigma, and the anti-Ig horseradish peroxidase detection kit was from BD Biosciences. mAb to syndecan-2 was produced by AdipoGen Inc. A portion of rat syndecan-2 cDNA representing the extracellular domain (S2E) was amplified by PCR and cloned upstream of human immunoglobulin heavy chain constant region (Fc) constructed in both pAGCF and pAGPCF2; the former utilized the natural leader sequence, whereas the latter used the plasminogen activator inhibitor-1 leader peptide. The Fc fusion constructs were transfected into human embryonic kidney 293 (HEK293) cells. DMEM serum-free medium was used to collect rat syndecan-2-Fc fusion protein from confluent cells for 2 days. The medium was harvested and spun down to remove cells, and the was to with The medium was with a and a A with and was with of constructs of rat were with fusion protein the polyclonal from the were from the and to mouse myeloma and cell were to the were from the were G. (clone syndecan-2 were and of the were by cell and that antibody the extracellular domain of both human and rat were with matrix 2 the was in 2 with 2 and with were and was were and remove samples were with as 15: PubMed Scopus Google Scholar). were human syndecan-2 or mouse a were and cloned into a of the are as human syndecan-2 human syndecan-2 mouse syndecan-2 sequence, mouse syndecan-2 sequence, syndecan-2 and the small interfering was purchased from Inc. from cells was used as for of cDNA were amplified using the rat syndecan-2 rat syndecan-2 rat rat the for of for for and for were The were in The amplified were cloned and to the PCR colon adenocarcinoma and human melanoma and mouse melanoma cells and and human fibrosarcoma cells were purchased from the Cell cells were in medium and cells were in DMEM and cells were in with fetal bovine serum with in in a were using Effectene or to the cells were with and with syndecan-2 cDNA for were by using one and of The were in Syndecan-2 expression was by using The were with and the cells were in 2 a The were by for with and by For of protein was with the antibody for 2 by with protein for were by The were and with The were by in tissue were with and by by the of in cells were in and were with antibody in in for times with cells were with antibody in in for Syndecan-2 expression was by was to well of a and the were to for The were in a and the were with in were to and the were in for The cells that to the surface of the were with and and For in invasion were with the of the membrane and with the For in metastasis melanoma cells were into a of On were and metastatic were were from patients in with the of the The were from the malignant and normal of patients the were in the and used for of from patients were in for in and for The were with and For the were and peroxidase activity was with and in by in and bovine serum for 2 The were for in antibody or antibody a with they were and with antibody in bovine serum for The were and with for by with and the were and with were with a Melanoma cells were tissue and one was in the of the using a the cells were with and in of the were various were as by K. H. R. M. Biol. 2008; PubMed Scopus Google Scholar). cells were with or in DMEM for and by with cells were in DMEM for cell or into 2 for to the of the was for melanin Cell was by a using as (3Park H. Kim Y. Lim Y. Han I. Oh E.S. J. Biol. Chem. 2002; 277: 29730-29736Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar). the role of syndecan-2 in the of human skin melanoma, the expression of syndecan-2 was in from and normal studies the of syndecan-2 expression in normal skin and On the other hand, we found that was increased syndecan-2 expression in nevus and Interestingly, syndecan-2 expression was increased in malignant melanomas and with melanoma in the and whereas serum for the melanin in the malignant melanoma with this elevated cell surface expression of syndecan-2 was observed in human melanoma cell lines data suggest that syndecan-2 expression is increased in human melanoma cells. Syndecan-2 is known to play a critical role as an adhesion during cell directly the role of syndecan-2 in the regulation of tumorigenic activity, we the of syndecan-2 expression melanoma cell melanoma cells were transfected with and a migration was with both cell migration and invasion were in cells in cells in In cell was decreased when syndecan-2 expression was by small interfering with the human melanoma cells, elevated cell surface expression of syndecan-2 was also observed in mouse melanoma cell lines Interestingly, cells levels of syndecan-2 cells Syndecan-2 overexpression enhanced the migration of mouse melanoma cells, migration and whereas cell migration decreased when syndecan-2 expression was by were observed using cells not of syndecan-2 expression by reduced metastatic potential of melanoma cells in strongly suggest that syndecan-2 regulates cell migration in melanoma regulates mouse melanoma cell or cells were with an and the cell surface expression levels of syndecan-2 were by was used as a were to as in the to cells were transfected with was and expression of syndecan-2 was by was used as the were with an and the cell surface expression levels of syndecan-2 were by was used as a migration were with cells transfected with 2 of the as in the to cells were transfected with and were was in the of the using a and of the were cells were transfected with syndecan-2 Cell surface expression levels of syndecan-2 were by was used as a were to as in the to cells were transfected with syndecan-2 A metastasis was as were and was using of both the and of lung are of is known to play a pivotal role in cancer cell migration L. Yang G.C. 1996; PubMed Scopus Google Scholar, L. L. E.T. Cancer Res. Google Scholar). we found that cellular phosphorylation was enhanced in melanoma cells. In phosphorylation of different and was in cells transfected with in cells transfected with the enhanced phosphorylation by in to stimulation of cell migration H. Han I. Kwon H.J. Oh E.S. Cancer Res. 2005; 65: PubMed Scopus Google Scholar), the membrane was and with antibodies or paxillin, a well known of M.D. Oncogene. 2001; PubMed Scopus Google Scholar). was the of and was the of suggesting of Indeed, expression increased phosphorylation of to regulate cell and phosphorylation of data that migration activity is associated with the of The previous the stimulatory of melanoma cell migration F. K. B. J. C. H. E. G. M. C. Exp. Dermatol. 2003; PubMed Scopus Google Scholar). In with increased cell caused increased cell surface expression of syndecan-2 suggesting that syndecan-2 expression correlates with cell is used as a in growth for human melanocytes P. A. Dermatol. Res. PubMed Scopus Google Scholar). In to reduced cell surface expression of syndecan-2 and melanoma cell migration the that syndecan-2 expression correlates with melanoma cell are a of peptides produced by cells in the of the pituitary M. 2004; PubMed Scopus Google Scholar). peptides are known to melanoma cell migration K. H. R. M. Biol. 2008; PubMed Scopus Google Scholar). we syndecan-2 expression in melanoma cells. decreased and cell surface protein expression of syndecan-2 with reduced syndecan-2 caused reduced migration and invasion of melanoma cells and whereas cell was not by during Furthermore, syndecan-2 overexpression rescued the migration defects induced by these suggest that melanoma cell migration reduced expression of syndecan-2 and the that syndecan-2 expression plays a crucial role in melanoma cell melanoma cell migration reduced expression of cells transfected with the or cDNA were with for Syndecan-2 expression levels and cell migration were as in the to of The of melanin is by in the skin, and eye A.G. C.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of and of various (e.g. which a in melanin J.C. C. E. K. R. Proc. Natl. Acad. Sci. U.S.A. 2007; PubMed Scopus Google Scholar). Therefore, we melanin plays a role in the cell migration of melanoma cells. with previous J. K. M. H. Saiki I. 1997; Google Scholar), enhanced the melanin of melanoma cells by whereas melanin was reduced by with the by K. H. R. M. Biol. 2008; PubMed Scopus Google Scholar). In syndecan-2 expression decreased in to with but not in to in cell migration with reduced syndecan-2 whereas of activity not melanoma cells migration Therefore, appears that regulates cell migration of the melanin Cell migration is a critical in tumor invasion and of cancer We that elevated syndecan-2 expression is crucial for tumorigenic activity in colon carcinoma and fibrosarcoma cells (3Park H. Kim Y. Lim Y. Han I. Oh E.S. J. Biol. Chem. 2002; 277: 29730-29736Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar, H. Han I. Kwon H.J. Oh E.S. Cancer Res. 2005; 65: PubMed Scopus Google Scholar). Here, we for the tumorigenic activity of syndecan-2 using melanoma, one of the most highly invasive types of with previous in colon carcinoma and fibrosarcoma cells, we syndecan-2 expression in tissue samples from both nevus and malignant human melanomas but not in normal melanocytes Similarly, syndecan-2 expression was elevated in melanoma cell lines Increased syndecan-2 expression correlates with increased melanoma cell whereas the opposite were observed when syndecan-2 expression was using and Therefore, syndecan-2 appears to as a in cancer cells. Although melanoma cell migration is associated with syndecan-2 is known the of regulation of melanoma cell that enhanced plays a role in the regulation of cell Overexpression of syndecan-2 increased phosphorylation of and H. L. D. Cancer Res. 2007; PubMed Scopus Google Scholar) that the invasion and metastatic of melanoma cells is by elevated expression and enhanced via and of is an that to the domain of also may play an role in the migration of melanoma cells. and melanoma cells may with to the cell surface expression of syndecan-2 that appears to play a critical role in the migration of melanoma cells. Syndecan-1 is for the induction of tumor by the which expression of as and matrix C.M. F. J. S. M. 2000; PubMed Scopus Google Scholar). we found that not syndecan-2 expression not implying that the is not in the regulation of cell Interestingly, syndecan-2 expression was by a that melanin Previous studies have found that increased levels are associated with melanoma A.G. C.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. Y. A. M. M. J. Dermatol. PubMed Scopus Google Scholar). is also known to the of human and melanoma cells to the ECM O. J. Dermatol. Sci. Full Text PDF PubMed Scopus Google Scholar) and is a of invasion by highly invasive melanoma cells M. Y. A. M. M. J. Dermatol. PubMed Scopus Google Scholar, K. K. Int. J. Cancer. PubMed Scopus Google Scholar). suggest that regulate melanoma cell migration via reduced syndecan-2 expression Indeed, syndecan-2 expression and increased melanoma cell migration whereas or syndecan-2 expression and reduced melanoma cell migration Although the role for in melanoma cell migration suggest that regulation syndecan-2 expression by plays a crucial role in the migration of melanoma cells. studies have shown that a of increases the of human skin G. N. C. J.L. S. Dermatol. 2004; PubMed Scopus Google Scholar). Interestingly, syndecan-2 expression of melanin Therefore, may play roles in the regulation of syndecan-2 in cell and in the melanin In addition, has been known that melanoma cell migration induced by the tumor factor α N. R. P. T.L. A. S. J. Cancer. 2004; PubMed Scopus Google Scholar). has been also known that the of and and invasion of by melanoma cells J. K. M. H. Saiki I. 1997; Google Scholar). Therefore, we the that other to reduced syndecan-2 contribute to to reduced cell migration via In a cell surface heparan sulfate proteoglycan, plays a critical role in regulating the migratory potential of melanoma cells. In addition, regulates the expression of syndecan-2 of the melanin and reduces cell the of melanoma the role of syndecan-2 in melanoma cell migration may as to the metastatic potential of the cancer and may the for the of to the metastasis of melanoma cells.

Recently, the healthcare field has undergone rapid changes owing to the accumulation of health big data and the development of machine learning. Data mining research in the field of healthcare has different characteristics from those of other data analyses, such as the structural complexity of the medical data, requirement for medical expertise, and security of personal medical information. Various methods have been implemented to address these issues, including the machine learning model and cloud platform. However, the machine learning model presents the problem of opaque result interpretation, and the cloud platform requires more in-depth research on security and efficiency. To address these issues, this paper presents a recent technology for Internet-of-Things-based (IoT-based) health big data processing. We present a cloud-based IoT health platform and health big data processing technology that reduces the medical data management costs and enhances safety. We also present a data mining technology for health-risk prediction, which is the core of healthcare. Finally, we propose a study using explainable artificial intelligence that enhances the reliability and transparency of the decision-making system, which is called the black box model owing to its lack of transparency.