A Role of Agrin in Maintaining the Stability of Vascular Endothelial Growth Factor Receptor-2 during Tumor Angiogenesis
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.
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BibTeX
@article{njah2026role,
title = {{A Role of Agrin in Maintaining the Stability of Vascular Endothelial Growth Factor Receptor-2 during Tumor Angiogenesis}},
author = {Kizito Njah and Sayan Chakraborty and Beiying Qiu and Surender Arumugam and Anandhkumar Raju and Ajaybabu V. Pobbati and Manikandan Lakshmanan and Vinay Tergaonkar and Guillaume Thibault and Xiaomeng Wang and Wanjin Hong},
journal = {Cell Reports},
year = {2026},
month = sep,
doi = {10.1016/j.celrep.2019.06.036},
url = {https://hal.science/hal-05770377v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A Role of Agrin in Maintaining the Stability of Vascular Endothelial Growth Factor Receptor-2 during Tumor Angiogenesis
AU - Kizito Njah
AU - Sayan Chakraborty
AU - Beiying Qiu
AU - Surender Arumugam
AU - Anandhkumar Raju
AU - Ajaybabu V. Pobbati
AU - Manikandan Lakshmanan
AU - Vinay Tergaonkar
AU - Guillaume Thibault
AU - Xiaomeng Wang
AU - Wanjin Hong
PY - 2026
DA - 2026/09/30
JO - Cell Reports
DO - 10.1016/j.celrep.2019.06.036
UR - https://hal.science/hal-05770377v1
AB - 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.
SN - 2211-1247
SN - 2211-1247
ER -