Subramaniam Manish Mani, Chan Jason Yongsheng, Yeoh Khay Guan, Quek Timothy, Ito Kosei, Salto-Tellez Manuel
Cancer Science Institute of Singapore (CSI), National University of Singapore, Singapore.
Biochim Biophys Acta. 2009 Dec;1796(2):315-31. doi: 10.1016/j.bbcan.2009.07.004. Epub 2009 Aug 12.
A major goal of molecular biology is to elucidate the mechanisms underlying cancer development and progression in order to achieve early detection, better diagnosis and staging and novel preventive and therapeutic strategies. We feel that an understanding of Runt-related transcription factor 3 (RUNX3)-regulated biological pathways will directly impact our knowledge of these areas of human carcinogenesis. The RUNX3 transcription factor is a downstream effector of the transforming growth factor-beta (TGF-beta) signaling pathway, and has a critical role in the regulation of cell proliferation and cell death by apoptosis, and in angiogenesis, cell adhesion and invasion. We previously identified RUNX3 as a major gastric tumor suppressor by establishing a causal relationship between loss of function and gastric carcinogenesis. More recently, we showed that RUNX3 functions as a bona fide initiator of colonic carcinogenesis by linking the Wnt oncogenic and TGF-beta tumor suppressive pathways. Apart from gastric and colorectal cancers, a multitude of epithelial cancers exhibit inactivation of RUNX3, thereby making it a putative tumor suppressor in human neoplasia. This review highlights our current understanding of the molecular mechanisms of RUNX3 inactivation in the context of cancer development and progression.
分子生物学的一个主要目标是阐明癌症发生和发展的潜在机制，以实现早期检测、更好的诊断和分期以及新的预防和治疗策略。我们认为，了解与Runt相关的转录因子3（RUNX3）调控的生物学途径将直接影响我们对人类致癌作用这些领域的认识。RUNX3转录因子是转化生长因子-β（TGF-β）信号通路的下游效应器，在通过凋亡调节细胞增殖和细胞死亡以及在血管生成、细胞黏附和侵袭中起关键作用。我们之前通过建立功能丧失与胃癌发生之间的因果关系，将RUNX3鉴定为一种主要的胃肿瘤抑制因子。最近，我们通过连接Wnt致癌途径和TGF-β肿瘤抑制途径，表明RUNX3作为结肠癌发生的真正启动因子发挥作用。除了胃癌和结直肠癌外，许多上皮性癌症都表现出RUNX3失活，从而使其成为人类肿瘤形成中的一种假定肿瘤抑制因子。本综述重点介绍了我们目前对癌症发生和发展背景下RUNX3失活分子机制的理解。
