Tumor-Promoting Role of GNA14 in Colon Cancer Development.

Recent studies have shown that mutations in members of the G-protein α family contribute to the onset and progression of cancer. However, the role of GNA14 in CRC remains unknown. In this study, we examined the effect of GNA14 on CRC through genetic approaches in vitro and in vivo. We found that knockdown by small interfering RNA (siRNA) inhibited the proliferation of CRC cells SW403 and HT29. knockout mice developed normally without obvious abnormalities. However, the number of polyps in the small intestine was significantly reduced in knockout mice compared to control mice after mating with mice, a representative CRC mouse model. In particular, deletion of the inhibited polyp growth, especially in the distal end of the small intestine. Histological examination showed that knockout mice suppressed malignant tumor progression due to decreased proliferation and increased apoptosis in polyps compared to controls. In addition, knockdown in CRC cells resulted in downregulation of ERK phosphorylation and β-catenin and β-catenin phosphorylation at S675. Similarly, ERK phosphorylation and phospho-β-catenin phosphorylation at S675 were decreased in polyps of knockout mice. Collectively, these analyses show that GNA14 may accelerate CRC cell proliferation and malignant tumor progression through ERK and β-catenin pathways.