The disparate role of BMP in stem cell biology

Abstract

Stem cells share several characteristics of cancer cells including loss of contact inhibition and immortality. Therefore, stem cells represent an excellent model system in which to define the molecular mechanisms underlying cancer development and progression. Several signal transduction pathways including leukemia inhibitory factor, Wnt and FGF have been demonstrated to function in stem cell self-renewal and differentiation. However, more recently bone morphogenetic proteins (BMPs) have emerged as key regulators of stem cell fate commitment. Intriguingly, BMPs have disparate roles in regulating the biology of embryonic stem (ES) cells compared with neural crest stem cells (NCSCs). Furthermore, although BMPs block neural differentiation of ES cells from both mouse and human, they contribute to self-renewal specifically in mouse ES cells. These observations strongly suggest that combinations of extracellular factors regulate stem cells, and that crosstalk between intracellular signaling pathways precisely defines stem cell fate commitment. In this review, we focus on the role of BMP signaling in mouse and human ES cells compared with NCSCs. We then discuss how the molecular effectors of BMP signaling may contribute to cancer, and thus represent potential targets for therapeutic intervention.

Identification of NOG as a Specific Breast Cancer Bone Metastasis-supporting Gene

“…Reinitiation at Bone-BMPs have been shown to prevent stem cell renewal of the neural crest and intestinal epithelia stem cells (22). Because NOGGIN is an antagonist of the BMP pathway, NOG expression by tumor cells might block its differentiation and enhance the capacity of metastatic cells to migrate, invade, and reinitiate lesions.…”

“…Next, we aimed to address the mechanistic contribution of NOG to the reinitiation process. We measured in tumorspheres the expression levels of ID1 and ID2, two well known targets of the BMP pathway that contribute to cell growth, senescence, and negatively regulating differentiation (22), and we also measured the levels of RANK, recently described to be key in the expansion of the mammary stem cell compartment in normal breast epithelial cells and in cancer (23,24) and upstream of ID2 (25). There was no significant difference in ID1 levels between groups, whereas the levels of ID2 and RANK changed according to NOG levels (Fig.…”

Induction of estrogen receptor α-36 expression by bone morphogenetic protein 2 in breast cancer cell lines

“…BMPs were identified based on their ability to promote ectopic cartilage and bone formation (2). BMPs function through conserved type I and type II transmembrane receptors and Smad-dependent and -independent pathways, to regulate a range of biological processes in a highly context-dependent manner (1,(3)(4)(5). Disruption of these pathways can lead to various diseases including cancer (6).…”

Comparative integromics on BMP/GDF family

“…WNT, Notch, FGF, Hedgehog, and BMP signaling pathways network together during embryogenesis, tissue regeneration, and carcinogenesis (1)(2)(3)(4)(5)(6)(7)(8). Canonical WNT signals are transduced through Frizzled receptors and LRP5/6 co-receptors to activate transcription of target genes, such as FGF18, FGF20, DKK1 and DKK4, based on the transcriptional complex consisting of TCF/LEF, ß-catenin, BCL9/BCL9L, and PYGO1/ PYGO2 (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”