title: Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma.
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 cell-derived 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.
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Chase
authors.initials: C
authors.lastname: Taylor
authors.affiliation: Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Holli A
authors.initials: HA
authors.lastname: Loomans
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Gregoire F
authors.initials: GF
authors.lastname: Le Bras
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Rainelli B
authors.initials: RB
authors.lastname: Koumangoye
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Alejandra I
authors.initials: AI
authors.lastname: Romero-Morales
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Quast
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.|Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.|Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.|Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Zaika
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.|Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.|Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.|Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Wael
authors.initials: W
authors.lastname: El-Rifai
authors.affiliation: Division of Dermatology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Andl
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.|Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.|Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.|Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Andl
mesh_terms: D028341:Activins / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D001471:Barrett Esophagus / Q000473:pathology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology
chemical_list: C422405:activin A; D028341:Activins
keywords: Barrett's esophagus; SOX9; esophageal adenocarcinoma