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Title: A role of Agrin in maintaining the stability of vascular endothelial growth factor receptor-2 during tumor angiogenesis
Authors: Njah, Kizito
Chakraborty, Sayan
Qiu, Beiying
Arumugam, Surender
Raju, Anandhkumar
Pobbati, Ajaybabu V.
Lakshmanan, Manikandan
Tergaonkar, Vinay
Thibault, Guillaume
Wang, Xiaomeng
Hong, Wanjin
Keywords: Agrin
Tumor Angiogenesis
Science::Biological sciences
Issue Date: 2019
Source: Njah, K., Chakraborty, S., Qiu, B., Arumugam, S., Raju, A., Pobbati, A. V., . . . Hong, W. (2019). A role of Agrin in maintaining the stability of vascular endothelial growth factor receptor-2 during tumor angiogenesis. Cell Reports, 28(4), 949-965. doi:10.1016/j.celrep.2019.06.036
Series/Report no.: Cell Reports
Abstract: Endothelial cell (EC) recruitment is central to the vascularization of tumors. Although several proteoglycans have been implicated in cancer and angiogenesis, their roles in EC recruitment and vascularization during tumorigenesis remain poorly understood. Here, we reveal that Agrin, which is secreted in liver cancer, promotes angiogenesis by recruiting ECs within tumors and metastatic lesions and facilitates adhesion of cancer cells to ECs. In ECs, Agrin-induced angiogenesis and adherence to cancer cells are mediated by Integrin-β1, Lrp4-MuSK pathways involving focal adhesion kinase. Mechanistically, we uncover that Agrin regulates VEGFR2 levels that sustain the angiogenic property of ECs and adherence to cancer cells. Agrin attributes an ECM stiffness-based stabilization of VEGFR2 by enhancing interactions with Integrin-β1-Lrp4 and additionally stimulates endothelial nitric-oxide synthase (e-NOS) signaling. Therefore, we propose that cross-talk between Agrin-expressing cancer and ECs favor angiogenesis by sustaining the VEGFR2 pathway.
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2019.06.036
Rights: © 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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