Year: 2015
Type: article
Abstract: // Chase Taylor 1, * , Holli A. Loomans 2, * , Gregoire F. Le Bras 1 , Rainelli B. Koumangoye 1 , Alejandra I. Romero-Morales 1 , Laura L. Quast 1 , Alexander I. Zaika 1, 2, 3, 4 , Wael El-Rifai 1, 2, 3, 4 , Thomas Andl 5 , Claudia D. Andl 1, 2, 3, 4 1 Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA 2 Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA 3 Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA 4 Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA 5 Division of Dermatology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA * These authors have contributed equally to this work Correspondence to: Claudia D. Andl, e-mail: [email protected] Keywords: Barrett's esophagus, esophageal adenocarcinoma, SOX9 Received: March 11, 2015 Accepted: September 24, 2015 Published: October 06, 2015 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.
Source: Oncotarget
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Awards: G2268269956, G286300149, G3433274139, The Molecular Functions of APE1 in Barrett's Tumorigenesis, Mechanisms of epithelial-mesenchymal crosstalk during esophageal cell invasion, Mechanisms of Tumorigenic Transformation of Barretts Esophagus, G5445507262, G5853943267, G7359148462, G7520984233, G7642566612, The role of Activin A signaling in esophageal cell invasion, G8616801171, Molecular and Cellular Basis for Digestive Diseases, New carcinogenic mechanisms of Helicobacter pylori infection, Cancer Center Support Grant
OpenAlex ID: W2174026431