RESUMEN
UNLABELLED: The mechanism underlying the progression of normal esophageal mucosa to esophageal adenocarcinoma remains elusive. WNT5A is a noncanonical WNT, which mainly functions via the receptor tyrosine kinase-like orphan receptor 2 (ROR2), and has an unclear role in carcinogenesis. In this study, we aimed to determine the role of WNT5A/ROR2 signaling in esophageal adenocarcinoma. Analysis of WNT5A and ROR2 expression patterns in healthy controls, Barrett and esophageal adenocarcinoma patients' esophageal clinical specimens as well as in various esophageal cell lines demonstrated a ROR2 overexpression in esophageal adenocarcinoma tissues compared with Barrett and healthy mucosa, whereas WNT5A expression was found significantly downregulated toward esophageal adenocarcinoma formation. Treatment of esophageal adenocarcinoma OE33 cells with human recombinant WNT5A (rhWNT5A) significantly suppressed proliferation, survival, and migration in a dose-dependent fashion. rhWNT5A was found to inhibit TOPflash activity in ROR2 wild-type cells, whereas increased TOPflash activity in ROR2-knockdown OE33 cells. In addition, ROR2 knockdown alone abolished cell proliferation and weakened the migration properties of OE33 cells. These findings support an early dysregulation of the noncanonical WNT5A/ROR2 pathway in the pathogenesis of esophageal adenocarcinoma, with the loss of WNT5A expression together with the ROR2 overexpression to be consistent with tumor promotion. IMPLICATIONS: The dysregulation of WNT5A/ROR2 noncanonical WNT signaling in Barrett-associated esophageal adenocarcinoma introduces possible prognostic markers and novel targets for tailored therapy of this malignancy. Mol Cancer Res; 14(7); 647-59. ©2016 AACR.
Asunto(s)
Adenocarcinoma/metabolismo , Esófago de Barrett/metabolismo , Neoplasias Esofágicas/metabolismo , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Proteína Wnt-5a/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Esófago de Barrett/patología , Proliferación Celular/fisiología , Progresión de la Enfermedad , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
This article is a report of the impact of an innovative assignment within an upper-division gerontology course in a public university. Although designed to enhance the understanding of important aging concepts for students in a Family Studies program, analysis of student writings revealed an increased understanding of the actual subject matter-older adults. As an addition to typical classroom instruction methods, students were paired with senior citizens from an adult education computer course to exchange a series of e-mail communications over the duration of the gerontology course. The e-mail discussion prompts stemmed from important concepts explored in class units. To determine the impact of this assignment, students were asked to submit a reflection paper on their experience. Student participants indicated that the experience enhanced their understanding of the course concepts and provided a positive interaction opportunity with older partners.