Procadherin17,A Novel Methyiation Controlled Tumor Supprcssor Gene In Gastric And Colorectal Cancer

Gastric and colorectal cancers are among the most common cancers and causes of cancer mortality worldwide, while epigenetic disruption of tumor suppressor genes (TSGs) is a fundamental contributor to their pathogenesis.Purpose:We studied the inactivation of a novel candidate TSG PCDH17through promoter methylation, and explored its functions in the pathogenesis of these cancers.Methods:PCDH17methylation was evaluated by methylation-specific PCR and bisulfite genome sequencing. PCDH17expression was determined by quantitative RT-PCR and immunohistochemistry. The effects of PCDH17on the growth and migration of tumor cells were tested in vitro and in vivo.Results:PCDH17was methylated in all tumor cell lines with silenced or reduced expression, also in all tumors but not in any normal gastric or colonic mucosa tissue. While PCDH17protein expression was high in normal gastric and colonic mucosa, it was absent in most gastric and colorectal tumor samples. Only16.7%(6/36) of gastric and16%(8/50) of colorectal tumors showed weak expression relative to normal mucosa. PCDH17protein expression was significantly correlated with low tumor stage (P=0.027) and less lymph node metastasis (P=0.039) in colorectal cancer. Restoring PCDH17expression inhibited tumor cell growth in vitro and in vivo, promoted apoptosis, and induced autophagy as confirmed by increased number of autophagic vacuoles and increased expression of autophagic proteins Atg-5, Atg-12, and LC3B II. Conclusions:PCDH17acts as a tumor suppressor and its methylation is a frequent, cancer-specific event that may serve as a biomarker for tumor diagnosis and risk assessment. Restoring PCDH17expression strongly reduced colony formation and induced both apoptosis and autophagy in tumor cells.