BMP2 as a promising anticancer approach: functions and molecular mechanisms

Invest New Drugs. 2022 Dec;40(6):1322-1332. doi: 10.1007/s10637-022-01298-4. Epub 2022 Aug 30.

Abstract

Bone morphogenetic protein 2 (BMP2), a pluripotent factor, is a member of the transforming growth factor-beta (TGF-β) superfamily and is implicated in embryonic development and postnatal homeostasis in tissues and organs. Experimental research in the contexts of physiology and pathology has indicated that BMP2 can induce macrophages to differentiate into osteoclasts and accelerate the osteolytic mechanism, aggravating cancer cell bone metastasis. Emerging studies have stressed the potent regulatory effect of BMP2 in cancer cell differentiation, proliferation, survival, and apoptosis. Complicated signaling networks involving multiple regulatory proteins imply the significant biological functions of BMP2 in cancer. In this review, we comprehensively summarized and discussed the current evidence related to the modulation of BMP2 in tumorigenesis and development, including evidence related to the roles and molecular mechanisms of BMP2 in regulating cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), cancer angiogenesis and the tumor microenvironment (TME). All these findings suggest that BMP2 may be an effective therapeutic target for cancer and a new marker for assessing treatment efficacy.

Keywords: BMP2; CSCs; EMT; TGF-β, SMAD; TME.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 2* / metabolism
  • Bone Morphogenetic Protein 2* / pharmacology
  • Cell Differentiation
  • Epithelial-Mesenchymal Transition
  • Humans
  • Signal Transduction
  • Transforming Growth Factor beta*

Substances

  • Bone Morphogenetic Protein 2
  • Transforming Growth Factor beta
  • BMP2 protein, human