FOXM1 is a downstream target of LPA and YAP oncogenic signaling pathways in high grade serous ovarian cancer

摘要: // Qipeng Fan 1 , Qingchun Cai Yan Xu Department of Obstetrics and Gynecology, Indiana University School Medicine, Indianapolis, IN 46202, USA Correspondence to: Xu, e-mail: xu2@iupui.edu Keywords: EOC (epithelial ovarian cancer), FOXM1, HGSC (high grade serous LPA (lysophosphatidic acid), YAP (yes-associated protein) Received: April 14, 2015      Accepted: June 01, Published: 13, 2015 ABSTRACT Lysophosphatidic acid (LPA), a prototypical ligand for G protein coupled receptors, Forkhead box M1 (FOXM1), transcription factor that regulates expression wide array genes involved in cancer initiation progression, are two important oncogenic signaling molecules human epithelial cancers (EOC). We conducted vitro mechanistic studies using pharmacological inhibitors, genetic forms the molecules, RNAi-mediated gene knock-down to uncover molecular mechanisms how these interact cells. Additionally, vivo mouse were performed confirm functional involvement FOXM1 tumor formation progression. show first time up-regulates active splice variants time- dose-dependent manner cell lines OVCA433, CAOV3, OVCAR5. i -PI3K-AKT 12/13 -Rho-YAP pathways both receptor (LPA 1–3 ) mediated up-regulation at transcriptional level. In addition, down-regulation CAOV3 xenografts significantly reduced ascites formation, metastasis, target proliferation, migration, or invasion. Collectively, our data link oncolipid LPA, oncogene YAP, central regulator proliferation/mutagenesis Moreover, results provide further support importance as potential therapeutic targets EOC.