Fig. 3
From: Targeting chemoresistant colorectal cancer via systemic administration of a BMP7 variant
BMP7v hampers the self-renewal and recapitulates a CD44v6−-like cell subpopulation profile. a Colony forming efficiency percentage of CD44v6+ CR-CSCs treated for 14 days with vehicle, gremlin or noggin alone or in combination with BMP4 or BMP7v. Data are reported as mean ± SD of five different CRC sphere cell lines analyzed (CSC#1, 2, 4, 7, and 10). Representative soft-agar analysis is shown in the lower part of graph. b Heat map of EMT-, tumor metastasis-, and Wnt pathway-related genes (2−ΔΔCt expression values) in spheres, CD44v6− and CD44v6+ cells. Data are presented as normalized expression values of three different CRC sphere cell lines (CSC#4, 8, and 18). c Log fold change (logFC) values of differentially expressed related genes in enriched CD44v6+ cells treated with BMP7v for 3 days. Data are presented as the average of normalized mRNA expression levels of four different CR-CSC lines (CSC#1, 3, 5, and 7). Dotted lines represent −1 and 1 logFC values. P value indicates difference between normalized mRNA expression levels of untreated vs BMP7v treated samples. d Venn diagram showing upregulated (red) and e downregulated (green) genes in CD44v6− and BMP7v treated cells. (Lower panels) Top ten significantly enriched gene sets (FDR q value ≤ 0.05), selected by using Hallmark, KEGG, and GO, related to the indicated 7 up- and 48 down-regulated genes common in CD44v6− cells and CD44v6+ cells treated with BMP7v. P values related to each enriched gene set are indicated. f Fold change values of the differentially upregulated (red) and downregulated (green) genes further validated by RT-PCR in CR-CSCs upon treatment with BMP7v for 72 h. Data are expressed as mean ± SD of experiments performed in CSC# 1, 3, 9, and 21
