The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
An oncogenic role of Agrin in regulating focal adhesion integrity in hepatocellular carcinoma
Open accessAbstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The identity and role of cell surface molecules driving complex biological events leading to HCC progression are poorly understood, hence representing major lacunae in HCC therapies. Here, combining SILAC quantitative proteomics and biochemical approaches, we uncover a critical oncogenic role of Agrin, which is overexpressed and secreted in HCC. Agrin enhances cellular proliferation, migration and oncogenic signalling. Mechanistically, Agrin’s extracellular matrix sensor activity provides oncogenic cues to regulate Arp2/3-dependent ruffling, invadopodia formation and epithelial–mesenchymal transition through sustained focal adhesion integrity that drives liver tumorigenesis. Furthermore, Agrin signalling through Lrp4-muscle-specific tyrosine kinase (MuSK) forms a critical oncogenic axis. Importantly, antibodies targeting Agrin reduced oncogenic signalling and tumour growth in vivo. Together, we demonstrate that Agrin is frequently upregulated and important for oncogenic property of HCC, and is an attractive target for antibody therapy.
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Cites
The basics of epithelial-mesenchymal transition
Kalluri, R., & Weinberg, R. A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39104 · Cited by 10,196
Microenvironmental regulation of tumor progression and metastasis
Quail, D. F., & Joyce, J. A. (2013) · Nature Medicine · doi:10.1038/nm.3394 · Cited by 7,994
LRP4 serves as a coreceptor of Agrin
Zhang, B., Luo, S., Wang, Q., Suzuki, T., Xiong, W. C., & Mei, L. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.006 · Cited by 525
Choi, H. Y., Liu, Y., Tennert, C., Sugiura, Y., Karakatsani, A., Kröger, S., Johnson, E. B., Hammer, R. E., Lin, W., & Herz, J. (2013) · eLife · doi:10.7554/elife.00220 · Cited by 71
Cited by
Role of Extracellular Matrix in Development and Cancer Progression
Walker, C., Mojares, E., & Del Río Hernández, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103028 · Cited by 1,084
The extracellular matrix as a multitasking player in disease
Theocharis, A. D., Manou, D., & Karamanos, N. K. (2019) · The FEBS Journal · doi:10.1111/febs.14818 · Cited by 511
Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis
Zhao, Y.-Q., Deng, X.-W., Xu, G.-Q., Lin, J., Lu, H.-Z., & Chen, J. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1183808 · Cited by 71
Self-citationA synergistic regulation works in matrix stiffness-driven invadopodia formation in HCC
Zhang, X., Zhao, Y., Li, M., Wang, M., Qian, J., Wang, Z., Wang, Y., Wang, F., Guo, K., Gao, D., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2023.216597 · Cited by 35
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Metadata
- Authors
- Chakraborty, S., Lakshmanan, M., Swa, H. L. F., Chen, J., Zhang, X., Ong, Y. S., Loo, L. S., Akıncılar, S. C., Gunaratne, J., Tergaonkar, V., Hui, K. M., & Hong, W.
- Venue
- Nature Communications
- Published
- 2015-01-29
- Volume
- 6
- Issue
- 1
- Pages
- 6184-6184
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2005674747
- Cited by
- 162
- References
- 4
- FWCI
- 8.82
- Type
- journal article
- Language
- en
- Open access
- gold
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- Chakraborty, S., Lakshmanan, M., Swa, H. L. F., Chen, J., Zhang, X., Ong, Y. S., Loo, L. S., Akıncılar, S. C., Gunaratne, J., Tergaonkar, V., Hui, K. M., & Hong, W. (2015). An oncogenic role of Agrin in regulating focal adhesion integrity in hepatocellular carcinoma. Nature Communications. https://doi.org/10.1038/ncomms7184
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