Dapper homolog 1 alpha suppresses metastasis ability of gastric cancer through inhibiting planar cell polarity pathway.
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.
Departments of Surgery, First Affiliated Hospital, Hebei Medical University, Shijiazhuang, China.
Yuegeng
Y
Liu
Departments of Surgery, First Affiliated Hospital, Hebei Medical University, Shijiazhuang, China.
Jingwan
J
Zhang
Endoscopy Center, First Affiliated Hospital, Hebei Medical University, Shijiazhuang, China.
Weifang
W
Yu
Departments of Surgery, First Affiliated Hospital, Hebei Medical University, Shijiazhuang, China.
Xiaoming
X
Zhang
Departments of Surgery, First Affiliated Hospital, Hebei Medical University, Shijiazhuang, China.
Guiqi
G
Wang
Departments of Surgery, First Affiliated Hospital, Hebei Medical University, Shijiazhuang, China.
Zengren
Z
Zhao
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D000066670:Cell Plasticity; D049109:Cell Proliferation; D048430:Cell Shape; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D016016:Proportional Hazards Models; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C491683:DACT1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins
DACT1α; gastric cancer; metastasis; tumor suppressor