Abstract 3912: GDF2 promotes anoikis susceptibility in ovarian and breast epithelia

Resistance to anchorage independent cell death (anoikis) is one of the features of metastasis and can be regulated by a diverse array of growth factors. The protein encoded by GDF2 is BMP9 and is a member of the Bone Morphogenetic protein family and the TGFβ superfamily with defined roles in angiogenesis and emerging yet controversial roles in carcinogenesis. We used normal and oncogenic epithelial systems to examine the role of GDF2 in ovarian and breast epithelia. We find that both normal and transformed epithelial cells are competent to activate the Smad1/5 signaling cascade in response to GDF2. This activation occurs via specific complex formation between the Type I receptor Serine threonine kinases Alk3 and Alk6 and the Type II receptor serine threonine kinase BMPRII. We find that in breast and ovarian epithelial cells GDF2 specifically regulates anchorage independent growth by increasing anoikis sensitivity that is dependent on GDF29s ability to sustain SMAD1/5 activation via Alk3 and Alk6. Analysis of cell lines and patient data indicates epigenetic regulation of GDF2 expression in ovarian and breast cancers. These findings reveal an antimetastatic role for GDF2 in ovarian and breast cancer models of disease with significant implications for the use of epigenetic drugs currently in clinical trials. Citation Format: Archana Varadaraj, Pratik Patel, Anne Serrao, Tirthankar Bandyopadhyay, Nam Y. Lee, Amir Jazaeri, Susan Murphy, Karthikeyan Mythreye. GDF2 promotes anoikis susceptibility in ovarian and breast epithelia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3912. doi:10.1158/1538-7445.AM2015-3912