title: Sema3E/plexin-D1 mediated epithelial-to-mesenchymal transition in ovarian endometrioid cancer.
abstract: Cancer cells often employ developmental cues for advantageous growth and metastasis. Here, we report that an axon guidance molecule, Sema3E, is highly expressed in human high-grade ovarian endometrioid carcinoma, but not low-grade or other ovarian epithelial tumors, and facilitates tumor progression. Unlike its known angiogenic activity, Sema3E acted through Plexin-D1 receptors to augment cell migratory ability and concomitant epithelial-to-mesenchymal transition (EMT). Sema3E-induced EMT in ovarian endometrioid cancer cells was dependent on nuclear localization of Snail1 through activation of phosphatidylinositol-3-kinase and ERK/MAPK. RNAi-mediated knockdown of Sema3E, Plexin-D1 or Snail1 in Sema3E-expressing tumor cells resulted in compromised cell motility, concurrent reversion of EMT and diminished nuclear localization of Snail1. By contrast, forced retention of Snail1 within the nucleus of Sema3E-negative tumor cells induced EMT and enhanced cell motility. These results show that in addition to the angiogenic effects of Sema3E on tumor vascular endothelium, an EMT strategy could be exploited by Sema3E/Plexin-D1 signaling in tumor cells to promote cellular invasion/migration.
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chun-Hsien
authors.initials: CH
authors.lastname: Tseng
authors.forename: Karl D
authors.initials: KD
authors.lastname: Murray
authors.forename: Mu-Fan
authors.initials: MF
authors.lastname: Jou
authors.forename: Su-Ming
authors.initials: SM
authors.lastname: Hsu
authors.forename: Hwai-Jong
authors.initials: HJ
authors.lastname: Cheng
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Huang
mesh_terms: D018269:Carcinoma, Endometrioid / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008648:Mesoderm / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms; D039961:Semaphorins / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C493082:PLXND1 protein, human; D020033:Protein Isoforms; C494123:SEMA3E protein, human; D039961:Semaphorins