Runx3 in Immunity, Inflammation and Cancer.

Joseph Lotem, Ditsa Levanon, Varda Negreanu, Omri Bauer, Shay Hantisteanu, Joseph Dicken, Yoram Groner

Advances in experimental medicine and biology 2017

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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.

Citation

Joseph Lotem, Ditsa Levanon, Varda Negreanu, Omri Bauer, Shay Hantisteanu, Joseph Dicken, Yoram Groner. Runx3 in Immunity, Inflammation and Cancer. Advances in experimental medicine and biology. 2017;962:369-393