The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters
Open accessAbstract
Vascular disruption induced by interactions between tumor-secreted permeability factors and adhesive proteins on endothelial cells facilitates metastasis. The role of tumor-secreted C-terminal fibrinogen-like domain of angiopoietin-like 4 (cANGPTL4) in vascular leakiness and metastasis is controversial because of the lack of understanding of how cANGPTL4 modulates vascular integrity. Here, we show that cANGPTL4 instigated the disruption of endothelial continuity by directly interacting with 3 novel binding partners, integrin α5β1, VE-cadherin, and claudin-5, in a temporally sequential manner, thus facilitating metastasis. We showed that cANGPTL4 binds and activates integrin α5β1-mediated Rac1/PAK signaling to weaken cell–cell contacts. cANGPTL4 subsequently associated with and declustered VE-cadherin and claudin-5, leading to endothelial disruption. Interfering with the formation of these cANGPTL4 complexes delayed vascular disruption. In vivo vascular permeability and metastatic assays performed using ANGPTL4-knockout and wild-type mice injected with either control or ANGPTL4-knockdown tumors confirmed that cANGPTL4 induced vascular leakiness and facilitated lung metastasis in mice. Thus, our findings elucidate how cANGPTL4 induces endothelial disruption. Our findings have direct implications for targeting cANGPTL4 to treat cancer and other vascular pathologies.
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Cites
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Joyce, J. A., & Pollard, J. W. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2618 · Cited by 3,684
Genes that mediate breast cancer metastasis to lung
Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., Viale, A., Olshen, A. B., Gerald, W. L., & Massagué, J. (2005) · Nature · doi:10.1038/nature03799 · Cited by 2,922
Lung metastasis genes couple breast tumor size and metastatic spread
Minn, A. J., Gupta, G. P., Padua, D., Bos, P., Nguyen, D. X., Nuyten, D., Kreike, B., Zhang, Y., Wang, Y., Ishwaran, H., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701138104 · Cited by 400
The role of integrins in the maintenance of endothelial monolayer integrity.
Lampugnani, M. G., Resnati, M., Dejana, E., & Marchisio, P. C. (1991) · The Journal of cell biology · doi:10.1083/jcb.112.3.479 · Cited by 292
Chong, H. C., Tan, M. J., Philippe, V., Tan, S. H., Tan, C. K., Ku, C. W., Goh, Y. Y., Wahli, W., Michalik, L., & Tan, N. S. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200809028 · Cited by 107
Self-citation
Cited by
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Setyawati, M. I., Tay, C. Y., Bay, B. H., & Leong, D. T. (2017) · ACS Nano · doi:10.1021/acsnano.7b01744 · Cited by 282
Self-citationRole of hypoxia-inducible factors in breast cancer metastasis
Gilkes, D. M., & Semenza, G. L. (2013) · Future Oncology · doi:10.2217/fon.13.92 · Cited by 274
Effects of Angiopoietin-2-Blocking Antibody on Endothelial Cell–Cell Junctions and Lung Metastasis
Holopainen, T., Saharinen, P., D’Amico, G., Lampinen, A., Eklund, L., Sormunen, R., Anisimov, A., Zarkada, G., Lohela, M., Heloterä, H., et al. (2012) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djs009 · Cited by 216
Angiopoietin-Like Proteins in Angiogenesis, Inflammation and Cancer
Carbone, C., Piro, G., Merz, V., Simionato, F., Santoro, R., Zecchetto, C., Tortora, G., & Melisi, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020431 · Cited by 200
Metadata
- Authors
- Huang, R.-L., Teo, Z., Chong, H. C., Zhu, P., Tan, M. J., Tan, C. K., Lam, C. R. I., Sng, M. K., Leong, D. T. W., Tan, S. M., Kersten, S., Ding, J. L., Li, H. Y., & Tan, N. S.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-10-06
- Volume
- 118
- Issue
- 14
- Pages
- 3990-4002
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2057253189
- Cited by
- 281
- References
- 5
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Huang, R.-L., Teo, Z., Chong, H. C., Zhu, P., Tan, M. J., Tan, C. K., Lam, C. R. I., Sng, M. K., Leong, D. T. W., Tan, S. M., Kersten, S., Ding, J. L., Li, H. Y., & Tan, N. S. (2011). ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters. Blood. https://doi.org/10.1182/blood-2011-01-328716
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