Sema3E/plexin-D1 mediated epithelial-to-mesenchymal transition in ovarian endometrioid cancer

Chun Hsien Tseng, Karl D Murray, Mu Fan Jou, Su Ming Hsu, Hwai-Jong Cheng, Pei Hsin Huang

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere19396
JournalPLoS One
Volume6
Issue number4
DOIs
StatePublished - 2011

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Epithelial-Mesenchymal Transition
ovarian neoplasms
Ovarian Neoplasms
Tumors
Cells
Neoplasms
cell movement
neoplasms
Cell Movement
Phosphatidylinositol 3-Kinase
phosphatidylinositol 3-kinase
endothelium
blood vessels
axons
Endometrioid Carcinoma
metastasis
carcinoma
Aptitude
Vascular Endothelium
RNA Interference

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sema3E/plexin-D1 mediated epithelial-to-mesenchymal transition in ovarian endometrioid cancer. / Tseng, Chun Hsien; Murray, Karl D; Jou, Mu Fan; Hsu, Su Ming; Cheng, Hwai-Jong; Huang, Pei Hsin.

In: PLoS One, Vol. 6, No. 4, e19396, 2011.

Research output: Contribution to journalArticle

Tseng, Chun Hsien ; Murray, Karl D ; Jou, Mu Fan ; Hsu, Su Ming ; Cheng, Hwai-Jong ; Huang, Pei Hsin. / Sema3E/plexin-D1 mediated epithelial-to-mesenchymal transition in ovarian endometrioid cancer. In: PLoS One. 2011 ; Vol. 6, No. 4.
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