Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma

Chase Taylor, Holli A. Loomans, Gregoire F. Le Bras, Rainelli B. Koumangoye, Alejandra I. Romero-Morales, Laura L. Quast, Alexander I. Zaika, Wael El-Rifai, Thomas Andl, Claudia D. Andl

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

TGFβ signaling has been implicated in the metaplasia from squamous epithelia to Barrett's esophagus and, ultimately, esophageal adenocarcinoma. The role of the family member Activin A in Barrett's tumorigenesis is less well established. As tumorigenesis is influenced by factors in the tumor microenvironment, such as fibroblasts and the extracellular matrix, we aimed to determine if epithelial cellderived Activin affects initiation and progression differently than Activin signaling stimulation from a mimicked stromal source. Using Barrett's esophagus cells, CPB, and the esophageal adenocarcinoma cell lines OE33 and FLO-1, we showed that Activin reduces colony formation only in CPB cells. Epithelial cell overexpression of Activin increased cell migration and invasion in Boyden chamber assays in CPB and FLO-1 cells, which exhibited mesenchymal features such as the expression of the CD44 standard form, vimentin, and MT1-MMP. When grown in organotypic reconstructs, OE33 cells expressed E-cadherin and Keratin 8. As mesenchymal characteristics have been associated with the acquisition of stem cell-like features, we analyzed the expression and localization of SOX9, showing nuclear localization of SOX9 in esophageal CPB and FLO-1 cells. In conclusion, we show a role for autocrine Activin signaling in the regulation of colony formation, cell migration and invasion in Barrett's tumorigenesis.

Original languageEnglish (US)
Pages (from-to)34228-34244
Number of pages17
JournalOncotarget
Volume6
Issue number33
DOIs
StatePublished - 2015

Keywords

  • Barrett's esophagus
  • Esophageal adenocarcinoma
  • SOX9

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Taylor, C., Loomans, H. A., Le Bras, G. F., Koumangoye, R. B., Romero-Morales, A. I., Quast, L. L., Zaika, A. I., El-Rifai, W., Andl, T., & Andl, C. D. (2015). Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma. Oncotarget, 6(33), 34228-34244. https://doi.org/10.18632/oncotarget.5349