Prof. Yoshiaki ITO Cancer Science Institute Singapore Link to biosketch

Abstract

Rapidly proliferating stem cells are known to reside at the isthmus of the stomach corpus. We identified IQGAP3 as a key marker of these proliferating stem cells, through its strict co-expression with the proliferation marker Ki67 and its requirement for the maintenance of stem cell property (Matsuo et al, GUT, 2020). IQGAP3 is an embryonic gene, encoding a cytoskeletal protein with multiple domains, which offers extensive interactions with the key components of growth signalling pathways.

We note the dramatic induction of IQGAP3 expression in terminally differentiated chief cells and the subsequent loss of cell identity when the mouse stomach was injured. RNA expression profiling of such cells revealed enhanced Myc expression as well as characteristics resembling early stage of gastric cancer. These chief cells may be in half way towards early stage of cancer.

We reported earlier that RUNX3 and APC may function independently as gatekeeper of carcinogenesis (Ito K et al, Cancer Cell, 2008). However, studies on the role of RUNX3 in carcinogenesis have been hampered by frequent promoter hypermethylation of RUNX3 gene and extremely low mutation frequency. Interestingly, however, we recently found that RUNX3 proteolytically degrades Myc strongly. Since RUNX3 is a transcription factor, we were surprised to see this phenomenon. We are examining whether this is the molecular basis of gatekeeper function of RUNX3.