title: Runx3 at the interface of immunity, inflammation and cancer.
abstract: Inactivation of tumor suppressor genes (TSG) in normal cells provides a viability/growth advantage that contributes cell-autonomously to cancer. More than a decade ago claims arose that the RUNX3 member of the RUNX transcription factor family is a major TSG inactivated in gastric cancer, a postulate extended later to other cancers. However, evidence that Runx3 is not expressed in normal gastric and other epithelia has challenged the RUNX3-TSG paradigm. Here we critically re-appraise this paradigm in light of recent high-throughput, quantitative genome-wide studies on thousands of human samples of various tumors and new investigations of the role of Runx3 in mouse cancer models. Collectively, these studies unequivocally demonstrate that RUNX3 is not a bona fide cell-autonomous TSG. Accordingly, RUNX3 is not recognized as a TSG and is not included among the 2000 cancer genes listed in the "Cancer Gene Census" or "Network for Cancer Genes" repositories. In contrast, RUNX3 does play important functions in immunity and inflammation and may thereby indirectly influence epithelial tumor development.
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: joseph.lotem@weizmann.ac.il.
authors: Joseph
authors: J
authors: Lotem
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Ditsa
authors: D
authors: Levanon
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Varda
authors: V
authors: Negreanu
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Omri
authors: O
authors: Bauer
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Shay
authors: S
authors: Hantisteanu
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Joseph
authors: J
authors: Dicken
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Yoram
authors: Y
authors: Groner
mesh_terms: D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000276:immunology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human
keywords: Cancer; DNA methylation; Immunity; Inflammation; RUNX3; Tumor suppressor gene