Fig. 3. Netrin-1 blockade triggers apoptosis and EMT inhibition in a preclinical mouse model.
a, Quantification of cell death using cleaved caspase-3 IHC in control (n = 8) and NP137 (n = 13)-treated tumours of CreERT2+/−Pten f/f mice. Bars are mean ± s.e.m.; *P = 0.0389 by Mann–Whitney two-sided test. b, Representative images of cleaved caspase-3 staining of a. Scale bar, 100 µm. c, Relative mRNA expression of EpCAM epithelial marker by RT–qPCR in mouse tumours, control (n = 5) and NP137 (n = 9). Bars are mean ± s.e.m., data normalized to HPRT gene; *P = 0.032 by Mann–Whitney two-sided test. d, Percentage of EpCAM high-expressing cells in control tumours (n = 4) versus NP137-treated (n = 7) as assessed by IHC. Bars are mean ± s.e.m.; **P = 0.0061 by Mann–Whitney two-sided test. e, EMT score (mouse orthologues of epithelial (epith.) or mesenchymal (mes.) signature from ref. 20) analysis derived from RNA-seq data, between control (n = 3) and NP137 (n = 3)-treated mice. Bars are mean ± s.e.m.; *P = 0.05 by Mann–Whitney one-sided test. f, Heatmap derived from RNA-seq data showing expression of EMT genes; control (n = 3) and NP137 (n = 3). Note that epithelial genes were upregulated under NP137-treated condition whereas mesenchymal genes were downregulated.