Vogiatzi Paraskevi, De Falco Giulia, Claudio Pier Paolo, Giordano Antonio
Department of Human Pathology and Oncology, Department of Molecular Biology, Medical Genetics Unit, University of Siena, Siena, Italy.
Cancer Biol Ther. 2006 Apr;5(4):371-4. doi: 10.4161/cbt.5.4.2748. Epub 2006 Apr 30.
RUNX3 is the oldest known gene in the RUNX family. Data have demonstrated its function to be thoroughly involved the neurogenesis of the dorsal root ganglia, T-cell differentiation and tumorigenesis of gastric epithelium. As a TGF-beta target, RUNX3 protein is believed to be involved in TGF-beta-mediated tumor suppressor pathway; however, little is known about its role in apoptosis. According to recent data reported by Yamamura et al., (J Biol Chem 2006; 281:5267-76), RUNX3 interacts with FoxO3a/FKHRL1 expressed in gastric cancer cells to activate Bim and induce apoptosis. The cooperation between RUNX3 and the PI3K/Akt signaling pathway component FoxO3a/FKHRL1 suggests the putative role of RUNX3 in the homoeostasis of gastric cells and in stomach cancer control. Here we discuss recent breakthroughs in our understanding of the mechanisms of RUNX3 in gastric malignancy and comment on possible future trends and perspectives.
RUNX3是RUNX家族中已知最古老的基因。数据表明其功能全面参与背根神经节的神经发生、T细胞分化以及胃上皮的肿瘤发生。作为转化生长因子-β（TGF-β）的靶点，RUNX3蛋白被认为参与TGF-β介导的肿瘤抑制途径；然而，其在细胞凋亡中的作用却知之甚少。根据山村等人最近报道的数据（《生物化学杂志》2006年；281:5267 - 5276），RUNX3与胃癌细胞中表达的FoxO3a/FKHRL1相互作用，激活Bim并诱导细胞凋亡。RUNX3与PI3K/Akt信号通路成分FoxO3a/FKHRL1之间的协同作用表明RUNX3在胃细胞稳态和胃癌控制中可能发挥的作用。在此，我们讨论了在理解RUNX3在胃恶性肿瘤中的机制方面的最新突破，并对未来可能的趋势和前景进行了评论。
