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The cadherins are a family of cell surface glycoproteins responsible forcell adhesion which play an important role in cell morphology, contact inhibitionand signal transduction during tumorigenesis. Protocadherin 8 (PCDH8), a memberof the cadherin family, has been reported to act as a tumor suppressor involvedin oncogenesis in breast cancer. In this study, we aimed to investigate the epigeneticinactivation of PCDH8 and its tumor suppressor function in gastric cancer. Theexpression of PCDH8 was markedly reduced or silenced in gastric cancer cell linescompared with normal gastric cells or tissues. Methylation of the PCDH8 gene promoterwas observed in 100% (4/4) of cell lines and 55.38% (36/65) of the primary gastriccancer by methylation-specific PCR, but not in normal gastric mucosa (0/10). MethylatedPCDH8 was significantly associated with lymph node metastasis in a logistic regressionanalysis. The demethylation reagent 5-aza-2'-deoxycytidine was able to restoreor upregulate PCDH8 expression in gastric cancer cell lines. Ectopic expressionof PCDH8 in silenced gastric cancer cells significantly inhibited cell migrationand induced apoptosis. For the first time, our study demonstrates the epigeneticinactivation of PCDH8 by promoter methylation and its tumor suppressor functionin human gastric cancer. Thus, PCDH8 could be identified as a candidate tumorsuppressor in human gastric cancer.

Frequent silencing of protocadherin 8 by promoter methylation, a candidate tumor suppressor for human gastric cancer