title: Small molecule inhibitor of the bone morphogenetic protein pathway DMH1 reduces ovarian cancer cell growth.
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.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Hover
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Young
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Bhola
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA; Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wilson
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA; Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Dineo
authors.initials: D
authors.lastname: Khabele
authors.affiliation: Research Medicine, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA; Department of Medicine, Cardiovascular, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Hong
authors.affiliation: Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Harold L
authors.initials: HL
authors.lastname: Moses
authors.affiliation: Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: philip.owens@vanderbilt.edu.
authors.forename: Philip
authors.initials: P
authors.lastname: Owens
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D019485:Bone Morphogenetic Proteins; C583032:DMH1 compound; D011720:Pyrazoles; D011804:Quinolines; D052004:Bone Morphogenetic Protein Receptors; D002945:Cisplatin
keywords: BMP; BMPR1a; DMH1; Ovarian cancer; Platinum resistance