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

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

  • Cancer Lett. 2015 Nov 1;368(1):79-87. doi: 10.1016/j.canlet.2015.07.032.
Laura D Hover 1,  Christian D Young 2,  Neil E Bhola 2,  Andrew J Wilson 3,  Dineo Khabele 3,  Charles C Hong 4,  Harold L Moses 5,  Philip Owens 6
Affiliations

Affiliations

  • 1 Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA.
  • 2 Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 3 Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA; Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA.
  • 4 Research Medicine, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA; Department of Medicine, Cardiovascular, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • 5 Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 6 Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: philip.owens@vanderbilt.edu.
PMID: 26235139 DOI: 10.1016/j.canlet.2015.07.032
Abstract

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.

Keywords

BMP; BMPR1a; DMH1; Ovarian cancer; Platinum resistance.

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