CPEB1, a novel gene silenced in gastric cancer: a Drosophila approach.

BACKGROUND

Gastric cancer (GC) is a highly prevalent disease, being the fourth most common cancer and the second leading cause of cancer-associated deaths worldwide. Although many genes have been implicated in its development, many cases remain genetically unexplained. Hence, there is an urgent need to find new disease-related genes.

METHODS

A transgenic Drosophila model was used to screen for novel genes putatively involved in GC. The authors evaluated the expression of the most interesting candidates in GC cell lines and primary tumours by semi-quantitative reverse transcription PCR, dissected the molecular mechanisms responsible for the deregulation of the most relevant one, and analysed its functional role in vitro and in a chicken embryo model.

RESULTS

Six candidate genes were identified, of which cytoplasmic polyadenylation element binding protein 1 (CPEB1) was downregulated in all GC cell lines and in 11 of 12 primary GC tumours. The pivotal CPEB1 promoter CpG site was determined, and it was found that methylation at this 79th CpG site was associated with CPEB1 silencing in GC cell lines and primary tumours. It was also discovered that methylation of this site was significantly more prevalent in diffuse type GC (p=0.007) and in cases with lymph node metastases (p=0.042). In vitro, CPEB1 impaired invasion. Its antiangiogenic role was also discovered, which was associated with downregulation of MMP14 and VEGFA.

CONCLUSIONS

The first evidence of CPEB1 involvement in GC is presented, along with the molecular mechanism underlying the regulation of its expression and its potential role in invasion and angiogenesis.