How does the human RUNX3 gene induce apoptosis in gastric cancer? Latest data, reflections and reactions.
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.
Vogiatzi
Paraskevi
P
Department of Human Pathology and Oncology, Department of Molecular Biology, Medical Genetics Unit, University of Siena, Siena, Italy.
De Falco
Giulia
G
Claudio
Pier Paolo
PP
Giordano
Antonio
A
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D050677:Core Binding Factor Alpha 3 Subunit; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C493729:Runx3 protein, human; D019869:Phosphatidylinositol 3-Kinases