Pancreatic adenocarcinoma upregulated factor promotes metastasis by regulating TLR/CXCR4 activation

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dc.contributor.authorH D Park-
dc.contributor.authorY Lee-
dc.contributor.authorY K Oh-
dc.contributor.authorJ G Jung-
dc.contributor.authorYoung Woo Park-
dc.contributor.authorK Myung-
dc.contributor.authorK H Kim-
dc.contributor.authorSang Seok Koh-
dc.contributor.authorD S Lim-
dc.date.accessioned2017-04-19T09:21:20Z-
dc.date.available2017-04-19T09:21:20Z-
dc.date.issued2011-
dc.identifier.issn0950-9232-
dc.identifier.uri10.1038/onc.2010.401ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/9955-
dc.description.abstractPancreatic adenocarcinoma upregulated factor (PAUF) is overproduced in certain types of cancer. However, little is known of the tumorigenic function of PAUF. In this study, we report the X-ray crystal structure of PAUF and reveal that PAUF is a mammalian lectin normally found in plant lectins. We also identify PAUF as an endogenous ligand of Toll-like receptor 2 (TLR2) and TLR4 by screening extracellular domain receptor pools. We further confirmed the specificity of the PAUF-TLR2 interaction. PAUF induces extracellular signal-regulated kinase (ERK) phosphorylation and activates the IKK-Β-mediated TPL2/MEK/ERK signaling pathway through TLR2. In agreement with the result of TLR2-mediated ERK activation by PAUF, PAUF induces increased expression of the protumorigenic cytokines RANTES and MIF in THP-1 cells. However, PAUF does not fully activate I-B-α signaling pathways in THP-1 cells, and fails to translocate the p65 subunit of the nuclear factor-B (NF-B) complex into the nucleus, resulting in no NF-B activation. Surprisingly, we found that PAUF also associated with the CXC chemokine receptor (CXCR4)-TLR2 complex and inhibited CXCR4-dependent, TLR2-mediated NF-B activation. Together, these findings suggest that the new cancer-associated ligand, PAUF, may activate TLR-mediated ERK signaling to produce the protumorigenic cytokines, but inhibits TLR-mediated NF-B signaling, thereby facilitating tumor growth and escape from innate immune surveillance.-
dc.publisherSpringer-Nature Pub Group-
dc.titlePancreatic adenocarcinoma upregulated factor promotes metastasis by regulating TLR/CXCR4 activation-
dc.title.alternativePancreatic adenocarcinoma upregulated factor promotes metastasis by regulating TLR/CXCR4 activation-
dc.typeArticle-
dc.citation.titleOncogene-
dc.citation.number2-
dc.citation.endPage211-
dc.citation.startPage201-
dc.citation.volume30-
dc.contributor.affiliatedAuthorYoung Woo Park-
dc.contributor.affiliatedAuthorSang Seok Koh-
dc.contributor.alternativeName박희동-
dc.contributor.alternativeName이양순-
dc.contributor.alternativeName오윤경-
dc.contributor.alternativeName정준구-
dc.contributor.alternativeName박영우-
dc.contributor.alternativeName명경재-
dc.contributor.alternativeName김경희-
dc.contributor.alternativeName고상석-
dc.contributor.alternativeName임대식-
dc.identifier.bibliographicCitationOncogene, vol. 30, no. 2, pp. 201-211-
dc.identifier.doi10.1038/onc.2010.401-
dc.subject.keywordCXCR4-
dc.subject.keywordERK-
dc.subject.keywordNF-κB-
dc.subject.keywordPAUF-
dc.subject.keywordTLR-
dc.subject.keywordTPL2-
dc.subject.localCXCR4-
dc.subject.localERK-
dc.subject.localErk-
dc.subject.localNuclear factor-kappa B-
dc.subject.localnuclear factor κB-
dc.subject.localNf-κb-
dc.subject.localNF-kB-
dc.subject.localnuclear factor kappa B-
dc.subject.localNF-κB (nuclear factor kappa-B)-
dc.subject.localNF-kappaB-
dc.subject.localNuclear factor-κb-
dc.subject.localNF-κ B-
dc.subject.localNF-κB-
dc.subject.localNF-kappa B-
dc.subject.localNuclear factor κB (NF-κB)-
dc.subject.localNuclear factor κB-
dc.subject.localNFκB-
dc.subject.localNf-κB-
dc.subject.localNuclear factor-κB-
dc.subject.localnuclear factorκB-
dc.subject.localNuclear factor (NF)-κB-
dc.subject.localNuclear factor kappa B-
dc.subject.localnuclear factor-κB-
dc.subject.localNF-ΚB-
dc.subject.localNuclear factor-kappa B (NF-κB)-
dc.subject.localNuclear factor-kappaB-
dc.subject.localnuclear factor-kappaB-
dc.subject.localnuclear factor-kappaB (NF-κB)-
dc.subject.localNFkappaB-
dc.subject.localNuclear factor kappaB-
dc.subject.localPAUF-
dc.subject.localtoll-like receptors-
dc.subject.localToll-like receptor (TLR)-
dc.subject.localToll-like receptors-
dc.subject.localtoll-like receptor-
dc.subject.localTLR-
dc.subject.localtoll-like receptor (TLR)-
dc.subject.localToll-like receptor-
dc.subject.localTPL2-
dc.description.journalClassY-
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