Journal
CANCER LETTERS
Volume 368, Issue 1, Pages 79-87Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.07.032
Keywords
BMP; BMPR1a; DMH1; Ovarian cancer; Platinum resistance
Categories
Funding
- Department of Defense-Breast Cancer Research Program postdoctoral fellowship [BC087501]
- National Institutes of Health [R01 CA085492, R01 CA102162]
- Robert J. and Helen C. Kleberg Foundation
- T.J. Martell Foundation
- NIH [HL10440]
- VA Merit grant [BX000771]
- Vanderbilt-Ingram Cancer Center [P30 CA68485]
- Vanderbilt Digestive Disease Research Center [DK058404]
- NIH/NCI Vanderbilt Cancer Center Support Grant [2P30 CA068485-14]
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The bone morphogenetic protein (BMP) pathway belonging to the Transforming Growth Factor beta (TGFP) 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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