Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

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dc.citation.firstpage1147en_US
dc.citation.issueNumber3en_US
dc.citation.journalTitleThe Journal of Clinical Investigationen_US
dc.citation.lastpage1162en_US
dc.citation.volumeNumber125en_US
dc.contributor.authorChen, Yulongen_US
dc.contributor.authorTerajima, Masahikoen_US
dc.contributor.authorYang, Yananen_US
dc.contributor.authorSun, Lien_US
dc.contributor.authorAhn, Young-Hoen_US
dc.contributor.authorPankova, Danielaen_US
dc.contributor.authorPuperi, Daniel S.en_US
dc.contributor.authorWatanabe, Takeshien_US
dc.contributor.authorKim, Min P.en_US
dc.contributor.authorBlackmon, Shanda H.en_US
dc.contributor.authorRodriguez, Jaimeen_US
dc.contributor.authorLiu, Huien_US
dc.contributor.authorBehrens, Carmenen_US
dc.contributor.authorWistuba, Ignacio I.en_US
dc.contributor.authorMinelli, Rosalbaen_US
dc.contributor.authorScott, Kenen_US
dc.date.accessioned2016-02-05T18:38:33Zen_US
dc.date.available2016-02-05T18:38:33Zen_US
dc.date.issued2015en_US
dc.description.abstractEpithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde–derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde–derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma.en_US
dc.identifier.citationChen, Yulong, Terajima, Masahiko, Yang, Yanan, et al.. "Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma." <i>The Journal of Clinical Investigation,</i> 125, no. 3 (2015) American Society for Clinical Investigation: 1147-1162. http://dx.doi.org/10.1172/JCI74725.en_US
dc.identifier.doihttp://dx.doi.org/10.1172/JCI74725en_US
dc.identifier.urihttps://hdl.handle.net/1911/88401en_US
dc.language.isoengen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.titleLysyl hydroxylase 2 induces a collagen cross-link switch in tumor stromaen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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