Small molecule inhibitor of the bone morphogenetic protein pathway DMH1 reduces ovarian cancer cell growth.

Hover LD, Young CD, Bhola NE, Wilson AJ, Khabele D, Hong CC, Moses HL, Owens P
Cancer Lett. 2015 368 (1): 79-87

PMID: 26235139 · PMCID: PMC4554828 · DOI:10.1016/j.canlet.2015.07.032

The bone morphogenetic protein (BMP) pathway belonging to the Transforming Growth Factor beta (TGFβ) family of secreted cytokines/growth factors is an important regulator of cancer. BMP ligands have been shown to play both tumor suppressive and promoting roles in human cancers. We have found that BMP ligands are amplified in human ovarian cancers and that BMP receptor expression correlates with poor progression-free-survival (PFS). Furthermore, active BMP signaling has been observed in human ovarian cancer tissue. We also determined that ovarian cancer cell lines have active BMP signaling in a cell autonomous fashion. Inhibition of BMP signaling with a small molecule receptor kinase antagonist is effective at reducing ovarian tumor sphere growth. Furthermore, BMP inhibition can enhance sensitivity to Cisplatin treatment and regulates gene expression involved in platinum resistance in ovarian cancer. Overall, these studies suggest targeting the BMP pathway as a novel source to enhance chemo-sensitivity in ovarian cancer.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

MeSH Terms (16)

Antineoplastic Agents Bone Morphogenetic Protein Receptors Bone Morphogenetic Proteins Cell Proliferation Cisplatin Disease-Free Survival Drug Resistance, Neoplasm Female Gene Expression Regulation, Neoplastic Humans Ovarian Neoplasms Pyrazoles Quinolines Signal Transduction Spheroids, Cellular Tumor Cells, Cultured

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