BMP signaling and its paradoxical effects in tumorigenesis and dissemination

Abstract

Bone morphogenetic proteins (BMPs) play important roles in embryonic and postnatal development by regulating cell differentiation, proliferation, motility, and survival, thus maintaining homeostasis during organ and tissue development. BMPs can lead to tumorigenesis and regulate cancer progression in different stages. Therefore, we summarized studies on BMP expression, the clinical significance of BMP dysfunction in various cancer types, and the molecular regulation of various BMP-related signaling pathways. We emphasized on the paradoxical effects of BMPs on various aspects of carcinogenesis, including epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), and angiogenesis. We also reviewed the molecular mechanisms by which BMPs regulate tumor generation and progression as well as potential therapeutic targets against BMPs that might be valuable in preventing tumor growth and invasion.

Keywords: BMP signaling pathway; cancer stem cell; epithelial–mesenchymal transition; tumorigenesis.

Figure 1. Relevant pathways regulate the paradoxical effects of BMP signaling in tumors

BMP signaling influences cancer cell progression through canonical SMAD and non-SMAD signaling pathways. The canonical SMAD-signaling pathway functions as a stimulator for cancer progression. However, non-SMAD signaling pathways, including PI3K/AKT, MAPK, NF-κB, and JAK/STAT signaling pathways, play bidirectional roles in various cancers. BMP signaling can cause the activation and inactivation of these non-SMAD signaling pathways to promote or suppress tumor progression.