Augmented CPT1A Expression Is Associated with Proliferation and Colony Formation during Barrett's Tumorigenesis.

Obesity is a known risk factor for the development of gastroesophageal reflux disease (GERD), Barrett's Esophagus (BE) and the progression to esophageal adenocarcinoma. The mechanisms by which obesity contributes to GERD, BE and its progression are currently not well understood. Recently, changes in lipid metabolism especially in the context of a high fat diet have been linked to GERD and BE leading us to explore whether fatty acid oxidation plays a role in the disease progression from GERD to esophageal adenocarcinoma.

Activin A-mediated epithelial de-differentiation contributes to injury repair in an in vitro gastrointestinal reflux model.

Reflux esophagitis is a result of esophageal exposure to acid and bile during episodes of gastroesophageal reflux. Aside from chemical injury to the esophageal epithelium, it has been shown that acid and bile induce cytokine-mediated injury by stimulating the release of pro-inflammatory cytokines. During the repair and healing process following reflux injury, the squamous esophageal cells are replaced with a columnar epithelium causing Barrett's metaplasia, which predisposes patients to esophageal adenocarcinoma.

Association of TGFβ signaling with the maintenance of a quiescent stem cell niche in human oral mucosa.

A dogma in squamous epithelial biology is that proliferation occurs in the basal cell layer. Notable exceptions are squamous epithelia of the human oral cavity, esophagus, ectocervix, and vagina. In these human epithelia, proliferation is rare in the basal cell layer, and the vast majority of cells positive for Ki67 and other proliferation markers are found in para- and suprabasal cell layers.

Esophageal cancer: The latest on chemoprevention and state of the art therapies.

Esophageal cancer is currently the 8th most common cancer worldwide and the 6th leading cause of cancer-related mortality. Despite remarkable advances, the mortality for those suffering from esophageal cancer remains high, with 5-year survival rates of less than 20%. In part, because most patients present with late-stage disease, long-term survival even after resection and therapy is disappointingly low.

Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma.

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.

Concerted loss of TGFβ-mediated proliferation control and E-cadherin disrupts epithelial homeostasis and causes oral squamous cell carcinoma.

Although the etiology of squamous cell carcinomas of the oral mucosa is well understood, the cellular origin and the exact molecular mechanisms leading to their formation are not. Previously, we observed the coordinated loss of E-cadherin (CDH1) and transforming growth factor beta receptor II (TGFBR2) in esophageal squamous tumors. To investigate if the coordinated loss of Cdh1 and Tgfbr2 is sufficient to induce tumorigenesis in vivo, we developed two mouse models targeting ablation of both genes constitutively or inducibly in the oral-esophageal epithelium.

TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion.

The TGFβ signaling pathway is essential to epithelial homeostasis and is often inhibited during progression of esophageal squamous cell carcinoma. Recently, an important role for TGFβ signaling has been described in the crosstalk between epithelial and stromal cells regulating squamous tumor cell invasion in mouse models of head-and-neck squamous cell carcinoma (HNSCC). Loss of TGFβ signaling, in either compartment, leads to HNSCC however, the mechanisms involved are not well understood.

The regulation of cell-cell adhesion during epithelial-mesenchymal transition, motility and tumor progression.

Adherens junctions (AJs) are essential for the maintenance of epithelial homeostasis and a key factor in the regulation of cell migration and tumor progression. AJs maintain cell-cell adhesion by linking transmembrane proteins to the actin cytoskeleton. Additionally, they participate in recruitment of signaling receptors and cytoplasmic proteins to the membrane.

CD44 upregulation in E-cadherin-negative esophageal cancers results in cell invasion.

E-cadherin is frequently lost during epithelial-mesenchymal transition and the progression of epithelial tumorigenesis. We found a marker of epithelial-mesenchymal transition, CD44, upregulated in response to functional loss of E-cadherin in esophageal cell lines and cancer. Loss of E-cadherin expression correlates with increased expression of CD44 standard isoform.