title: Runx3 in Immunity, Inflammation and Cancer.
abstract: In this chapter we summarize the pros and cons of the notion that Runx3 is a major tumor suppressor gene (TSG). Inactivation of TSGs in normal cells provides a viability/growth advantage that contributes cell-autonomously to cancer. More than a decade ago it was suggested that RUNX3 is involved in gastric cancer development, a postulate extended later to other epithelial cancers portraying RUNX3 as a major TSG. However, evidence that Runx3 is not expressed in normal gastric and other epithelia has challenged the RUNX3-TSG paradigm. In contrast, RUNX3 is overexpressed in a significant fraction of tumor cells in various human epithelial cancers and its overexpression in pancreatic cancer cells promotes their migration, anchorage-independent growth and metastatic potential. Moreover, 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 have unequivocally demonstrated that RUNX3 is not a bona fide cell-autonomous TSG. Importantly, accumulating data demonstrated that RUNX3 functions in control of immunity and inflammation, thereby indirectly influencing epithelial tumor development.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lotem
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Ditsa
authors.initials: D
authors.lastname: Levanon
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Varda
authors.initials: V
authors.lastname: Negreanu
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Omri
authors.initials: O
authors.lastname: Bauer
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Hantisteanu
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.|Compugen Ltd, Holon, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Dicken
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel. yoram.groner@weizmann.ac.il.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
mesh_terms: D000818:Animals; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit
keywords: Cancer; Immunity; Inflammation; RUNX3; Tumor suppressor gene