The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma
Open accessAbstract
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.
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1 retracted
Procollagen lysyl hydroxylase 2 is essential for hypoxia-induced breast cancer metastasis
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RetractedPhosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
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Comprehensive molecular characterization of clear cell renal cell carcinoma
The Cancer Genome Atlas Research Network (2013) · Nature · doi:10.1038/nature12222 · Cited by 3,485
p21 in cancer: Intricate networks and multiple activities
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Gene-expression profiles predict survival of patients with lung adenocarcinoma
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Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K. J., & Werb, Z. (2020) · Nature Communications · doi:10.1038/s41467-020-18794-x · Cited by 2,296
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Burgstaller, G., Oehrle, B., Gerckens, M., White, E. S., Schiller, H. B., & Eickelberg, O. (2017) · European Respiratory Journal · doi:10.1183/13993003.01805-2016 · Cited by 482
Modulating extracellular matrix stiffness: A strategic approach to boost cancer immunotherapy
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Metadata
- Authors
- Chen, Y., Terajima, M., Yang, Y., Sun, L., Ahn, Y.-H., Pankova, D., Puperi, D. S., Watanabe, T., Kim, M. P., Blackmon, S. H., Rodriguez, J., Liu, H., Behrens, C., Wistuba, I. I., Minelli, R., Scott, K. L., Sanchez-Adams, J., Guilak, F., Pati, D., Thilaganathan, N., Burns, A. R., Creighton, C. J., Martinez, E. D., Zal, T., Grande-Allen, K. J., Yamauchi, M., & Kurie, J. M.
- Venue
- Journal of Clinical Investigation
- Published
- 2015-02-09
- Volume
- 125
- Issue
- 3
- Pages
- 1147-1162
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2169283220
- Cited by
- 181
- References
- 8
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Chen, Y., Terajima, M., Yang, Y., Sun, L., Ahn, Y.-H., Pankova, D., Puperi, D. S., Watanabe, T., Kim, M. P., Blackmon, S. H., Rodriguez, J., Liu, H., Behrens, C., Wistuba, I. I., Minelli, R., Scott, K. L., Sanchez-Adams, J., Guilak, F., Pati, D., . . . Kurie, J. M. (2015). Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma. Journal of Clinical Investigation. https://doi.org/10.1172/jci74725
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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