Runx3 in Immunity, Inflammation and Cancer

Adv Exp Med Biol. 2017:962:369-393. doi: 10.1007/978-981-10-3233-2_23.

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.

Keywords: Cancer; Immunity; Inflammation; RUNX3; Tumor suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Core Binding Factor Alpha 3 Subunit / genetics*
  • Humans
  • Immunity / genetics*
  • Inflammation / genetics*
  • Inflammation / pathology
  • Neoplasms / genetics*
  • Neoplasms / pathology*

Substances

  • Core Binding Factor Alpha 3 Subunit