Bmp2is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning

Molecular signatures of metaplastic carcinoma of the breast by large-scale transcriptional profiling: identification of genes potentially related to epithelial–mesenchymal transition

“…Despite their potential roles in the conventional type of breast cancer, how these genes participate in the pathophysiology of MCB remains to be clarified. BMP2, one of the TGF-b superfamily members, also plays a crucial role in EMT during cardiac cushion development (Ma et al, 2005). Since EMT is implicated in sarcomatous metaplasia of carcinoma cells in MCB (Thiery, 2002), the identification of BMP2 as an upregulated gene in MCB and in Snail 6SA-MCF7 cells that display features of EMT further highlights a potential role for BMP2 underlying the features of EMT in MCBs and hinges on its role in EMT during cardiac cushion development.…”

“…Notably, several of the 87 MCB-overexpressed genes were functionally related to extracellular matrix (ECM), including genes associated with ECM synthesis (PCOLCE2, PLOD, PLOD2, CSPG4, HAS, VIM and COL27A1), remodeling (CTSZ), adhesion/motility/migration (HAPLN1, VIM, COL9A3, COL9A1, CSPG4, KINDLIN 1 and FLNA), and genes associated with skeletal development and/or chondroossification (BMP2, CSPG4 and TNFRSF11 (osteoprotegrin)). BMP2, which also has documented function related to EMT (Ma et al, 2005), was identified among genes upregulated in MCBs. In contrast, genes encoding proteins related to maintaining epithelial phenotype, including cytoskeleton (KRT18 and KRT19), cell-cell adhesion molecules (CDH1, CEA-CAM6 and TACSTD1 (epithelial adhesion molecule)) and tight junction (EPPK1 (epiplakin 1), CLDN7, CRB3 and F11R (junctional adhesion molecule 1)), were downregulated in MCBs (Liu et al, 2000;Fujiwara et al, 2001;Lemmers et al, 2004).…”

BMP and FGF regulatory pathways in semilunar valve precursor cells

“…BMP and FGF signaling pathways have previously been shown to be important for normal heart development including endocardial cushion formation, cushion elongation, and remodeling (Galvin et al, 2000;Gaussin et al, 2002;Delot et al, 2003;Jiao et al, 2003;Sugi et al, 2003Sugi et al, , 2004Somi et al, 2004;Ma et al, 2005;Lincoln et al, 2006a). A number of BMP ligands have been identified in the developing heart; in particular, BMP4 is expressed in the OFT myocardium adjacent to the endocardial cushions during early stages of valve development (Keyes et al, 2003).…”

“…A number of BMP ligands have been identified in the developing heart; in particular, BMP4 is expressed in the OFT myocardium adjacent to the endocardial cushions during early stages of valve development (Keyes et al, 2003). The importance of BMP signaling during cushion formation is supported by studies identifying early roles for BMP ligand and receptors during EMT and formation of the OFT endocardial cushions, but further studies are required to confirm the in vivo role of BMP in valve precursor cells during valve maturation (Gaussin et al, 2002;Jiao et al, 2003;Ma et al, 2005). As shown for BMP2 in developing AV valve precursor cells (Lincoln et al, 2006a), the present studies show that BMP4 is sufficient to activate Smad 1/5/8 signaling.…”

Co-ordinating Notch, BMP, and TGF-β signaling during heart valve development

“…BMP ligands 2, 4, 5, 6, and 7 are all expressed in AVC and OFT myocardium during valve formation [39][40][41][42][43][44]. The BMP type I receptor, ALK2 is expressed in endocardium and a subset of mesenchymal cells in the heart at E10 [45].…”