The Yin and Yang of bone morphogenetic proteins in cancer

Abstract

Bone morphogenetic proteins (BMPs) were first studied as growth factors or morphogens of the transforming growth factor-beta superfamily. These growth molecules, originally associated with bone and cartilage development, are now known to play an important role in morphogenesis and homeostasis in many other tissues. More recently, significant contributions from BMPs, their receptors, and interacting molecules have been linked to carcinogenesis and tumor progression. On the other hand, BMPs can sometimes function as a tumor suppressor. Our report highlights these new roles in the pathogenesis of cancer that may suggest novel targets for therapeutic intervention.

Figure 1

Figure showing the involvement of various BMP molecules and their receptors in complex and multi-step molecular process of human cancer. The four outer circles are representing the events reported to be associated with progression of cancer. Outermost text boxes are showing a snapshot about the particular BMPs, BMPR, and the way these are involved in various cancerous processes either protectively or anti-protectively. These cancerous processes decides the fate of a living cell in its micro environment. Text box A, showing role of BMPs in EMT and MET; text box B, showing expression, over expression and copy number alteration in BMPs and BMPRs during cancer; text box C, showing BMPs during growth, proliferation, metastasis and angiogenesis; and text box D, showing the association of mutations, SNPs, microRNA with BMPs and their receptors and relation with epigenetic regulation during various human cancer. In the center of the figure the text CANCER and two symbol upward ( ) and downward triangle ( ), means these different BMPs may increase and decrease the incidence of human cancer in various cell, tissue and cancer type.

Figure 2

BMPs and their cancer and anti-cancer activities are described in a cancer cell. We hypothesize here that there is a delicate balance between the cancer and anti-cancer environment of a cells. BMP molecules, depending on their environmental stimuli can switch the delicate balance in either direction. Such balance is necessary for the survival, normal growth, and development of a cell. [Table 1 and 2]