The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation
Open accessAbstract
Lung metastasis is the major cause of breast cancer-related mortality. The neutrophil-associated inflammatory microenvironment aids tumor cells in metastatic colonization in lungs. Here, we show that tumor-secreted protease cathepsin C (CTSC) promotes breast-to-lung metastasis by regulating recruitment of neutrophils and formation of neutrophil extracellular traps (NETs). CTSC enzymatically activates neutrophil membrane-bound proteinase 3 (PR3) to facilitate interleukin-1β (IL-1β) processing and nuclear factor κB activation, thus upregulating IL-6 and CCL3 for neutrophil recruitment. In addition, the CTSC-PR3-IL-1β axis induces neutrophil reactive oxygen species production and formation of NETs, which degrade thrombospondin-1 and support metastatic growth of cancer cells in the lungs. CTSC expression and secretion are associated with NET formation and lung metastasis in human breast tumors. Importantly, targeting CTSC with compound AZD7986 effectively suppresses lung metastasis of breast cancer in a mouse model. Overall, our findings reveal a mechanism of how tumor cells regulate neutrophils in metastatic niches and support CTSC-targeting approaches for cancer treatment.
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Cites
Neutrophil Extracellular Traps Kill Bacteria
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Self-citationSpatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer
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Cited by
Neutrophil extracellular traps in homeostasis and disease
Wang, H., Kim, S. J., Lei, Y., Wang, S., Wang, H., Huang, H., Zhang, H., & Tsung, A. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01933-x · Cited by 537
Self-citationNeutrophil extracellular traps: from physiology to pathology
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Chen, Q., Li, Q., Liang, Y., Zu, M., Chen, N., Canup, B. S. B., Luo, L., Wang, C., Zeng, L., & Xiao, B. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.08.016 · Cited by 361
Self-citationTumor-associated neutrophils and neutrophil-targeted cancer therapies
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Therapeutic targeting of tumour myeloid cells
Barry, S. T., Gabrilovich, D. I., Sansom, O. J., Campbell, A. D., & Morton, J. P. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00546-2 · Cited by 305
Metadata
- Authors
- Xiao, Y., Cong, M., Li, J., He, D., Wu, Q., Tian, P., Wang, Y., Yang, S., Liang, C., Liang, Y., Wen, J., Liu, Y., Luo, W., Lv, X., He, Y., Cheng, D.-D., Zhou, T., Zhao, W., Zhang, P., Zhang, X., Xiao, Y., Qian, Y., Wang, H., Gao, Q., Yang, Q.-C., Yang, Q., & Hu, G.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 39
- Issue
- 3
- Pages
- 423-437.e7
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W3120670329
- Cited by
- 649
- References
- 74
- FWCI
- 31.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Xiao, Y., Cong, M., Li, J., He, D., Wu, Q., Tian, P., Wang, Y., Yang, S., Liang, C., Liang, Y., Wen, J., Liu, Y., Luo, W., Lv, X., He, Y., Cheng, D.-D., Zhou, T., Zhao, W., Zhang, P., . . . Hu, G. (2021). Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. Cancer Cell. https://doi.org/10.1016/j.ccell.2020.12.012
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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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