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dc.contributor.authorChen, Yulong
Terajima, Masahiko
Yang, Yanan
Sun, Li
Ahn, Young-Ho
Pankova, Daniela
Puperi, Daniel S.
Watanabe, Takeshi
Kim, Min P.
Blackmon, Shanda H.
Rodriguez, Jaime
Liu, Hui
Behrens, Carmen
Wistuba, Ignacio I.
Minelli, Rosalba
Scott, Ken
dc.date.accessioned 2016-02-05T18:38:33Z
dc.date.available 2016-02-05T18:38:33Z
dc.date.issued 2015
dc.identifier.citation Chen, Yulong, Terajima, Masahiko, Yang, Yanan, et al.. "Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma." The Journal of Clinical Investigation, 125, no. 3 (2015) American Society for Clinical Investigation: 1147-1162. http://dx.doi.org/10.1172/JCI74725.
dc.identifier.urihttps://hdl.handle.net/1911/88401
dc.description.abstract Epithelial 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.
dc.language.iso eng
dc.publisher American Society for Clinical Investigation
dc.rights Article 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.
dc.title Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma
dc.type Journal article
dc.contributor.funder National Institutes of Health
dc.contributor.funder Cancer Prevention Research Institute of Texas
dc.contributor.funder UT Lung Specialized Programs of Research Excellence
dc.contributor.funder U.S. Department of Defense
dc.contributor.funder MD Anderson Cancer Center
dc.citation.journalTitle The Journal of Clinical Investigation
dc.citation.volumeNumber 125
dc.citation.issueNumber 3
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1172/JCI74725
dc.identifier.pmcid PMC4362236
dc.identifier.pmid 25664850
dc.identifier.grantID R01 CA109478 (National Institutes of Health)
dc.identifier.grantID CA125123 (National Institutes of Health)
dc.identifier.grantID R01 CA125269 (National Institutes of Health)
dc.identifier.grantID R01 CA157450 (National Institutes of Health)
dc.identifier.grantID R21AR060978 (National Institutes of Health)
dc.identifier.grantID 1R21 CA184817-01 (National Ins
dc.type.publication publisher version
dc.citation.firstpage 1147
dc.citation.lastpage 1162


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