Overexpression of ESM1 increased the expression of DLL4 and promoted productive angiogenesis. (a) The protein interaction network was associated with ESM1 in the String Database. (b) Gene expression correlation between DLL4 and ESM1 in breast cancer was found in the TCGA database. (c) Western blotting for DLL4 in HUVEC cells with or without human ESM1 added (Figure S3). (d,e) Western blotting for DLL4 in MDA-MB-231-S, MDA-MB-231-S ovESM1, MDA-MB-231-R, or MDA-MB-231-RshESM1#1–3 (Figures S4 and S5). (f) Gene expression correlation between VEGFA and ESM1 in breast cancer was found in TCGA database. (g) Quantitative evaluation of DLL4, VEGFA, and MMP9 in MDA-MB-231-S or MDA-MB-231-S ovESM1 tumor sections from mice treated with PBS or bevacizumab. * p < 0.05; *** p < 0.001 by t test. (h) IOD of CD31 and α-SMA overlap region in MDA-MB-231-S or MDA-MB-231-S ovESM1 tumor sections from mice treated with PBS or bevacizumab. **** p < 0.0001 by t test.