title: Molecular pathology of RUNX3 in human carcinogenesis.
abstract: 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.
authors.affiliation: Cancer Science Institute of Singapore (CSI), National University of Singapore, Singapore.
authors.forename: Manish Mani
authors.initials: MM
authors.lastname: Subramaniam
authors.forename: Jason Yongsheng
authors.initials: JY
authors.lastname: Chan
authors.forename: Khay Guan
authors.initials: KG
authors.lastname: Yeoh
authors.forename: Timothy
authors.initials: T
authors.lastname: Quek
authors.forename: Kosei
authors.initials: K
authors.lastname: Ito
authors.forename: Manuel
authors.initials: M
authors.lastname: Salto-Tellez
mesh_terms: D000818:Animals; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000502:physiology*; D019175:DNA Methylation; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human