Tumor-secreted Anterior Gradient-2 Binds to VEGF and FGF2 and Enhances Their Activities by Promoting Their Homodimerization

Guo H, et al., doi: 10.1038/onc.2017.132, Oncogene, 2017

Human anterior gradient-2 (AGR2) is a protein that overexpresses in human adenocarcinomas. The exact function of secreted AGR2, including its mechanism of action is not well understood. Reported herein is the mechanism for the tumor-promoting function of extracellular AGR2. Furthermore, authors demonstrate that extracellular AGR2 directly binds to vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) and amplify their activities. Binding affinity of AGR2 to various growth factors were studied by using the Bio-Layer Interferometry (BLI). A Pall ForteBio Octet RED96 instrument equipped with Ni-NTA biosensors was used to perform all BLI experiments. Biosensor tips were immobilized with His-AGR2. Subsequently, the AGR2-loaded biosensor tips were dipped in solutions of VEGF121, VEGF165, VEGF189, FGF2, EGF, IGF-1 and TGFβ1, respectively. KD values were determined for all the binding interactions. Collectively, findings of this investigation suggest that the secreted AGR2 is a promising antitumor target, which affects the function of extracellular signaling networks.

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