Protocadherin20 Acts as a Tumor Suppressor Gene: Epigenetic Inactivation in Nasopharyngeal Carcinoma.
Genetic alterations of 13q21 (PCDH 8,9,17, and 20) are frequently observed in multiple tumors, suggesting the presence of critical tumor suppressor genes (TSGs). Protocadherin20 (PCDH20), located at 13q21.2, belongs to the δ1-protocadherins, which constitutes one of the largest subgroup within the adherin superfamily. Frequent downregulation/silencing of PCDH20 was found in NPC cell lines using semiquantitative PCR. PCDH20 mRNA was broadly expressed in normal nasopharyngeal tissues and cell lines. Promoter methylation of PCDH20 was observed in 80% (4/5) of NPC cell lines and 78.4% (40 of 51) of primary tumors by methylation-specific PCR, but rarely in normal nasopharygeal tissues and nasopharyngeal epithelial cell line (NP69). The silencing of PCDH20 can be reversed by pharmacological demethylation, indicating an epigenetic mechanism. Restoration of PCDH20 expression in NPC cells strongly suppressed cell numbers and colony formation. Overexpression of PCDH20 antagonized Wnt/β-catenin signaling pathway and promoted β-catenin to translocate from nucleus to cytoplasm and membrane. PCDH20 significantly inhibited the migration and invasion ability of NPC cells. PCDH20 also inhibited epithelial-mesenchymal transition (EMT) through enhanced expression of E-cadherin. Our study identified PCDH20 as a functional tumor suppressor and an important antagonist of Wnt/β-catenin signaling and EMT, with frequent epigenetic inactivation in NPC.
Department of Otolaryngology, The first Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Tao
T
Chen
Department of Otolaryngology, The first Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Biaoli
B
Long
Molecular Oncology and Epigenetics Laboratory, The first Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Guosheng
G
Ren
Molecular Oncology and Epigenetics Laboratory, The first Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Tingxiu
T
Xiang
Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
Lili
L
Li
Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
Zhaohui
Z
Wang
Department of Otolaryngology, The first Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Ya
Y
He
Department of Otolaryngology, The first Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Quan
Q
Zeng
Department of Otolaryngology, The first Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Suling
S
Hong
Department of Otolaryngology, The first Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, China.
Guohua
G
Hu
D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000091363:Protocadherins; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
D015820:Cadherins; D009419:Nerve Tissue Proteins; C000601912:PCDH20 protein, human; D000091363:Protocadherins; D025521:Tumor Suppressor Proteins
EPIGENETIC INACTIVATION; EPITHELIAL-MESENCHYMAL TRANSITION; METHYLATION; NASOPHARYNGEAL CARCINOMA; PROTOCADHERIN 20; TUMOR SUPPRESSOR GENE; Wnt/β-CATENIN