Bone morphogenetic protein 4—a fascinating regulator of cancer cell behavior

Abstract

Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor β (TGFβ) superfamily and are well-known for their indispensable roles in vertebrate development. In recent years, important new information has been generated on the contribution of BMP family members, such as BMP4, in cancer pathogenesis. First of all, BMP4 gene variants have been shown to predispose to colorectal cancer. In sporadic cancer, BMP4 expression levels are commonly altered in many tumor types and have been linked to patient prognosis in hepatocellular and ovarian cancer. In terms of BMP4 function in cancer cells, the majority of studies demonstrate that BMP4 suppresses cell growth both in vitro and in vivo, and at the same time is able to induce migration, invasion, and epithelial-mesenchymal transition. These latter phenotypes are typically associated with cancer metastasis and progression, and thus BMP4 seems to elicit effects that are both detrimental and beneficial for the cancer cells. The functional effects of BMP4 are not restricted to the control of cell proliferation and mobility, since it also contributes to the regulation of differentiation, apoptosis, and angiogenesis. The latter is especially intriguing since the formation of new blood vessels is a prerequisite for sustained tumor growth and cancer progression. Mainly due to its growth suppressive abilities, BMP4 has been suggested as a possible therapeutic target in cancer cells. However, the other functional characteristics of BMP4, especially the promotion of cell mobility, make such strategies less appealing. Improved knowledge of the downstream mediators of BMP4 effects in cancer cells may allow dissection of the different BMP4-induced phenotypes and thereby generation of specific targeted therapies.