Karen McLean1 and Ronald J. Buckanovich1, 2,*; 1Division of Gynecologic Oncology; Department of Obstetrics and Gynecology; University of Michigan; Ann Arbor, MI USA; 2Division of Hematology/Oncology; Department of Internal Medicine; University of Michigan; Ann Arbor, MI USA;* Email: ronaldbu@ umich. edu; http://dx. doi. org/10.4161/cc. 23553 stem cells, resulting in enhanced tumorigenesis. 5 BMP4 has also been shown to directly upregulate iD3 proto-oncogene expression in human ovarian cancer cells. 6 Additionally, exogenous BMP4 treatment of ovarian cancer cells results in epithelial-mesenchymal transition (EMT), with increased cellular adhesion, motility and invasion. 7 All of these studies support a pro-tumorigenic role of BMP overexpression in ovarian cancer (Fig. 1). These downstream effects of BMP signaling are consistent with the finding that overexpression of BMP2, a closely related family member of BMP4, is associated with poorer prognosis in ovarian cancer patients. 8 Ma et al. also extend the clinical implications of Lin28-mediated upregulation of BMP4 by looking at the prognostic implications of Lin28 overexpression. immunohistochemical analysis of more than 300 primary ovarian cancers, looking at the expression of Lin28 and the stem cell factor Oct4, demonstrated that overexpression of Lin28 and Oct4 together is correlated with decreased patient survival. 1 interestingly, Lin28 and Oct4 define a subset of cells in ovarian cancer with stem-like properties. 9 These findings, together with the role of BMPs in promoting ovarian cancer stemness, suggest an important interplay between Lin28/Oct4/BMP that impacts cancer stem cells, tumorigenesis and, ultimately, patient outcomes.

Ovarian cancer is a disease plagued by recurrences with progressive chemoresistance, ultimately leading to uncontrolled cancer growth resulting in patient death. The challenge that lies ahead is integrating our improved molecular understanding of ovarian cancer pathogenesis with novel therapeutic options to improve patient outcomes. Considering the BMP pathway, further studies are necessary to continue to tease out the relative roles of epithelial and stromal production of BMPs in ovarian cancer and the subsequent