The bone morphogenetic proteins (BMPs), a subgroup of the transforming growth factor-beta (TGF-beta) superfamily, are involved in multiple biological processes such as embryonic development and... Show moreThe bone morphogenetic proteins (BMPs), a subgroup of the transforming growth factor-beta (TGF-beta) superfamily, are involved in multiple biological processes such as embryonic development and maintenance of adult tissue homeostasis. The importance of a functional BMP pathway is underlined by various diseases, including cancer, which can arise as a consequence of dysregulated BMP signaling. Mutations in crucial elements of this signaling pathway, such as receptors, have been reported to disrupt BMP signaling. Next to that, aberrant expression of BMP antagonists could also contribute to abrogated signaling. In this review we set out to highlight how BMP antagonists affect not only the cancer cells, but also the other cells present in the microenvironment to influence cancer progression. Show less
The basis of the presented investigations in this thesis is the modulation of signal inducers and their respective activated signaling cascades through intrinsic antagonistic feedback- and/or feed... Show moreThe basis of the presented investigations in this thesis is the modulation of signal inducers and their respective activated signaling cascades through intrinsic antagonistic feedback- and/or feed forward-loops. In particular, signal inducers of the transforming growth factor-_ superfamily were investigated on their impact on tissue development and maintenance. Thereby, the main focus lies on a group of proteins that are known as bone morphogenetic proteins (BMPs). Due to their wide impact, Dr. H. Reddi recently proposed a more suitable name to this cytokines: body morphogenetic proteins. The distinct terminology is also reflected in this book. Not only does this book discuss the impact of BMP signal modulation on osteoblast differentiation, it also focuses on BMPs as potential inducers of signaling drifts in fibrotic traits. Interestingly, BMPs can relay signals with different outcomes. They can be signal triggers themselves as investigated in the case of osteoblast differentiation, but they can also arrest signaling cascades, as shown for TGF-_ induced fibrosis. Up to date, more than fifteen different BMPs are known. One aim of this book is to biochemically characterize different BMPs on their potential to relay signals and how this signals can be governed to yield a specific medical benefit. It is well known that BMPs are tightly regulated on diverse interfaces throughout the cell. Thereby, the presented investigations focus on innate extracellular signaling modulators, as well as on synthetic small molecule inhibitors that have the potential to facilitate the development of new treatment strategies of certain human diseases. Show less
