American Association for Cancer Research
15357163mct140836-sup-138654_1_supp_2854114_nksc8z.docx (1.77 MB)

Supplementary Figure S4 from Endostatin Has ATPase Activity, Which Mediates Its Antiangiogenic and Antitumor Activities

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journal contribution
posted on 2023-04-03, 14:28 authored by Shan Wang, Xin-an Lu, Peng Liu, Yan Fu, Lin Jia, Shunli Zhan, Yongzhang Luo

Supplementary Figure S4. Tryptophan emission fluorescence



Endostatin is an endogenous angiogenesis inhibitor with broad-spectrum antitumor activities. Although the molecular mechanisms of endostatin have been extensively explored, the intrinsic biochemical characteristics of endostatin are not completely understood. Here, we revealed for the first time that endostatin embedded novel ATPase activity. Moreover, mutagenesis study showed that the ATPase activity of endostatin mutants positively correlated with effects on endothelial cell activities and tumor growth. E-M, an endostatin mutant with higher ATPase activity than that of wild-type (WT) endostatin, significantly increased endostatin-mediated inhibitory effects on endothelial cell proliferation, migration, tube formation, and adhesion. In vivo study showed that E-M displayed enhanced antitumor effects compared with WT. On the other hand, K96A, K96R, and E176A, endostatin mutants with lower ATPase activities than that of WT, showed reduced or comparable effects on targeting both in vitro endothelial cell activities and in vivo tumor angiogenesis and tumor growth. Furthermore, endostatin and its mutants exhibited distinct abilities in regulations of gene expression (Id1, Id3), cell signaling (Erk, p38, and Src phosphorylation), and intracellular ATP levels. Collectively, our study demonstrates that endostatin has novel ATPase activity, which mediates its antiangiogenic and antitumor activities, suggesting that construction of endostatin analogues with high ATPase activity may provide a new direction for the development of more potent antiangiogenic drugs. Mol Cancer Ther; 14(5); 1192–201. ©2015 AACR.

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