Research Papers:
Dapper homolog 1 alpha suppresses metastasis ability of gastric cancer through inhibiting planar cell polarity pathway
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 2672 views | HTML 2610 views | ?
Abstract
Yuegeng Liu1, Jingwan Zhang1, Weifang Yu2, Xiaoming Zhang1, Guiqi Wang1, Zengren Zhao1
1Departments of Surgery, First Affiliated Hospital, Hebei Medical University, Shijiazhuang, China
2Endoscopy Center, First Affiliated Hospital, Hebei Medical University, Shijiazhuang, China
Correspondence to:
Zengren Zhao, email: [email protected]
Keywords: DACT1α, gastric cancer, metastasis, tumor suppressor
Received: September 20, 2016 Accepted: October 17, 2016 Published: November 09, 2016
ABSTRACT
Dapper homolog 1 alpha (DACT1α) is a member of DACT family and an important regulator in the planar cell polarity pathway. We aim to clarify its functional role in metastasis ability of gastric cancer. DACT1α was silenced in all gastric cancer cell lines (8/8), but expressed in normal gastric tissue. Ectopic expression of DACT1α in silenced gastric cancer cell lines (AGS, BGC823 and MGC803) by stable transfection significantly suppressed cancer cell spreading (P < 0.05), migration (P < 0.01) and invasion (P < 0.01). These effects were associated with downregulation of planar cell polarity pathway related genes involved in cell proliferation (PDGFB, VEGFA), adhesion (ITGA1, ITGA2, ITGA3, ITGB3) and migration/invasion (PLAU, MMP9, MCAM, Dvl-2 and JNK). DACT1α promoter methylation was detected in 205 gastric cancers and 20 normal controls by direct bisulfite genomic sequencing. DACT1α methylation was detected in 29.3% (60/205) of gastric cancer patients, but not in normal tissues. DACT1α methylation was associated with poor survival of gastric cancer patients. In conclusion, DACT1α plays a pivotal role as a potential tumor suppressor in migration and invasion of gastric cancer. DACT1α methylation may serve as a biomarker for the prognosis of gastric cancer.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 13234