The roles of Disabled-2 and TGF-β signaling pathway in esophageal squamous cell carcinomas

Abstract

Background: Patients with esophageal squamous cell carcinomas (ESCCs) have poor survival and frequently developed with synchronous head and neck squamous cell carcinomas (HNSCCs) Disabled-2 (DAB2) is a crucial tumor suppressor for multiple signaling pathways (ERK TGF-β etc ) and emerging evidences suggest TGF-β-induced regulatory T cells (Treg) enable tumor cells to escape immunosurveillance resulting in tumor progression We aimed to investigate the significance of DAB2 expression and Treg infiltration in ESCC and the field cancerization of esophagus at clinical and cellular levels Methods: Tumor tissues of 200 patients (100 ESCC only 50 HNSCC only and 50 synchronous SCCs) were evaluated for DAB2 expression and quantitatively accessed for the tumor infiltrating Treg by immunohistochemistry and then correlated to the clinical features Expressions of DAB2 ERK β-catenin E-cadherin and N-cadherin in ESCC cell lines and cell migration abilities were evaluated by western blot and wound healing assay respectively siRNA knockdown and over-expression studies were performed to validate the association between DAB2 and cell behavior The density of Treg was also correlated to the level of Treg-associated inhibitory cytokines (IL 10 IL-35 and TGF β) and chemokine (CCL22) To explore the upstream regulatory mechanism of DAB2 the methylation status of DAB2 promoter were analyzed by Methylation-specific PCR Results: Forty-five ESCC patients had low-DAB2 expression and significantly had larger tumor size deeper invasion depth lymph node metastasis worse survival and higher recurrence rate (P

Date of Award	2015 Aug 21
Original language	English
Supervisor	Bor-Shyang Sheu (Supervisor)