The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix
Open accessAbstract
Citrullination of proteins, a post-translational conversion of arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented in cancer. Here we show that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer (CRC). Using proteomics, we demonstrate that liver metastases exhibit higher levels of citrullination and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance for citrullination in metastatic growth is evident in murine models where inhibition of citrullination substantially reduces liver metastatic burden. Additionally, citrullination of a key matrix component collagen type I promotes greater adhesion and decreased migration of CRC cells along with increased expression of characteristic epithelial markers, suggesting a role for citrullination in promoting mesenchymal-to-epithelial transition and liver metastasis. Overall, our study reveals the potential for PAD4-dependant citrullination to drive the progression of CRC liver metastasis.
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Cites
The extracellular matrix: A dynamic niche in cancer progression
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Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis
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Stromal gene expression defines poor-prognosis subtypes in colorectal cancer
Calon, A., Lonardo, E., Berenguer-Llergo, A., Espinet, E., Hernando-Momblona, X., Iglesias, M., Sevillano, M., Palomo-Ponce, S., Tauriello, D. V. F., Byrom, D., et al. (2015) · Nature Genetics · doi:10.1038/ng.3225 · Cited by 1,070
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Cited by
Concepts of extracellular matrix remodelling in tumour progression and metastasis
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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Sun, L., Zhang, H., & Gao, P. (2022) · Protein & Cell · doi:10.1007/s13238-021-00846-7 · Cited by 770
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Li, J., Ma, X., Chakravarti, D., Shalapour, S., & DePinho, R. A. (2021) · Genes & Development · doi:10.1101/gad.348226.120 · Cited by 573
The Extracellular Matrix Modulates the Metastatic Journey
Kai, F., Drain, A. P., & Weaver, V. M. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.03.026 · Cited by 537
Colorectal liver metastasis: molecular mechanism and interventional therapy
Zhou, H., Liu, Z., Wang, Y., Wen, X., Amador, E. H., Yuan, L., Ran, X., Xiong, L., Ran, Y., Chen, W., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00922-2 · Cited by 298
Metadata
- Authors
- Yuzhalin, A. E., Gordon-Weeks, A. N., Tognoli, M. L., Jones, K., Markelc, B., Konietzny, R., Fischer, R., Muth, A., O’Neill, E., Thompson, P. R., Venables, P. J., Kessler, B. M., Lim, S. Y., & Muschel, R. J.
- Venue
- Nature Communications
- Published
- 2018-11-14
- Volume
- 9
- Issue
- 1
- Pages
- 4783-4783
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2899743407
- Cited by
- 188
- References
- 8
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- gold
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- Yuzhalin, A. E., Gordon-Weeks, A. N., Tognoli, M. L., Jones, K., Markelc, B., Konietzny, R., Fischer, R., Muth, A., O’Neill, E., Thompson, P. R., Venables, P. J., Kessler, B. M., Lim, S. Y., & Muschel, R. J. (2018). Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix. Nature Communications. https://doi.org/10.1038/s41467-018-07306-7
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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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