Oncogene database

1015

CDH17

cadherin 17, LI cadherin (liver-intestine);CDH17;cadherin 17, LI cadherin (liver-intestine)

HPT-1 cadherin|LI cadherin|LI-cadherin|cadherin-16|cadherin-17|human intestinal peptide-associated transporter HPT-1|human peptide transporter 1|intestinal peptide-associated transporter HPT-1|liver-intestine cadherin

8q22.1

protein-coding

Hepatocellular carcinoma (HCC) is a lethal malignancy for which there are no effective therapies. To develop rational therapeutic approaches for treating this disease, we are performing proof-of-principle studies targeting molecules crucial for the development of HCC. Here, we show that cadherin-17 (CDH17) adhesion molecule is up-regulated in human liver cancers and can transform premalignant liver progenitor cells to produce liver carcinomas in mice. RNA interference-mediated knockdown of CDH17 inhibited proliferation of both primary and highly metastatic HCC cell lines in vitro and in vivo. The antitumor mechanisms underlying CDH17 inhibition involve inactivation of Wnt signaling, because growth inhibition and cell death were accompanied by relocalization of beta-catenin to the cytoplasm and a concomitant reduction in cyclin D1 and an increase in retinoblastoma. CONCLUSION: Our results identify CDH17 as a novel oncogene in HCC and suggest that CDH17 is a biomarker and attractive therapeutic target for this aggressive malignancy.

Liver-intestine cadherin (CDH17) is a novel member of the cadherin superfamily implicated in gastric cancer progression. To determine the role of CDH17 in the process of gastric cancer invasive growth, in the present study, RNA interference mediated by recombinant lentivirus vectors expressing artificial CDH17 miRNA was applied to induce a long-lasting down-regulation of CDH17 gene expression in BGC823 cells. The expression levels of CDH17, tumor cell motility, migration potential, and pro-liferation were measured by flow cytometry, real-time RT-PCR, Western blot analysis, immunofluorescence staining, wound healing assay, and MTT assay, respectively. Results show that four recombinant plasmid expression vectors encoding pre-miRNA against CDH17, pcDNA-CDH17-miR-SR1, -SR2, -SR3, and -SR4 were constructed correctly and down-regulated the CDH17 mRNA levels by 5.5, 57, 91, and 98%, respectively, in BGC823 cells which had an overexpression of CDH17. We packaged the recombinant lentiviral vector for CDH17 RNA interference with pcDNA-CDH17-miR-SR4 which had the highest interfering efficiency and succeeded in construction of the stable transfectants. Of note, more than 90% knockdown of CDH17 expression in BGC823 cells was obtained by miRNA technique. The CDH17-miRNA-transfected cells showed significant decrease in cell proliferation, cell motility, and migration in comparison with the control cells. Thus, we proposed that CDH17 may be an oncogene up-regulating invasive features of gastric cancer cells and could be a hopeful target for the control of gastric cancer progression.