Dapper homolog 1 alpha suppresses metastasis ability of gastric cancer through inhibiting planar cell polarity pathway

Yuegeng Liu; Jingwan Zhang; Weifang Yu; Xiaoming Zhang; Guiqi Wang; Zengren Zhao

doi:10.18632/oncotarget.13234

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Research Papers:

Dapper homolog 1 alpha suppresses metastasis ability of gastric cancer through inhibiting planar cell polarity pathway

Yuegeng Liu, Jingwan Zhang, Weifang Yu, Xiaoming Zhang, Guiqi Wang and Zengren Zhao _

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Oncotarget. 2016; 7:81423-81434. https://doi.org/10.18632/oncotarget.13234

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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.

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PII: 13234

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Research Papers:

Dapper homolog 1 alpha suppresses metastasis ability of gastric cancer through inhibiting planar cell polarity pathway

Abstract