TY - JOUR
T1 - RUNX3 in Stem Cell and Cancer Biology
AU - Chuang, Linda Shyue Huey
AU - Matsuo, Junichi
AU - Douchi, Daisuke
AU - Bte Mawan, Nur Astiana
AU - Ito, Yoshiaki
N1 - Funding Information:
This work was supported by grants from the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centers of Excellence initiative, the Singapore Ministry of Health’s National Medical Research Council under its Clinician-Scientist Individual Research Grant (MOH-CIRG21jun-0003) and the National Medical Research Council’s Open Fund Large Collaborative Grant (OFLCG18May-0023), National University of Singapore School of Medicine (NUSMed) Internal Grant Funding (NUHSRO/2019/086/StomachStemCell and NUHSRO/2022/043/NUSMed/25/LOA) to Y.I.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/2
Y1 - 2023/2
N2 - The runt-related transcription factors (RUNX) play prominent roles in cell cycle progression, differentiation, apoptosis, immunity and epithelial–mesenchymal transition. There are three members in the mammalian RUNX family, each with distinct tissue expression profiles. RUNX genes play unique and redundant roles during development and adult tissue homeostasis. The ability of RUNX proteins to influence signaling pathways, such as Wnt, TGFβ and Hippo-YAP, suggests that they integrate signals from the environment to dictate cell fate decisions. All RUNX genes hold master regulator roles, albeit in different tissues, and all have been implicated in cancer. Paradoxically, RUNX genes exert tumor suppressive and oncogenic functions, depending on tumor type and stage. Unlike RUNX1 and 2, the role of RUNX3 in stem cells is poorly understood. A recent study using cancer-derived RUNX3 mutation R122C revealed a gatekeeper role for RUNX3 in gastric epithelial stem cell homeostasis. The corpora of RUNX3R122C/R122C mice showed a dramatic increase in proliferating stem cells as well as inhibition of differentiation. Tellingly, RUNX3R122C/R122C mice also exhibited a precancerous phenotype. This review focuses on the impact of RUNX3 dysregulation on (1) stem cell fate and (2) the molecular mechanisms underpinning early carcinogenesis.
AB - The runt-related transcription factors (RUNX) play prominent roles in cell cycle progression, differentiation, apoptosis, immunity and epithelial–mesenchymal transition. There are three members in the mammalian RUNX family, each with distinct tissue expression profiles. RUNX genes play unique and redundant roles during development and adult tissue homeostasis. The ability of RUNX proteins to influence signaling pathways, such as Wnt, TGFβ and Hippo-YAP, suggests that they integrate signals from the environment to dictate cell fate decisions. All RUNX genes hold master regulator roles, albeit in different tissues, and all have been implicated in cancer. Paradoxically, RUNX genes exert tumor suppressive and oncogenic functions, depending on tumor type and stage. Unlike RUNX1 and 2, the role of RUNX3 in stem cells is poorly understood. A recent study using cancer-derived RUNX3 mutation R122C revealed a gatekeeper role for RUNX3 in gastric epithelial stem cell homeostasis. The corpora of RUNX3R122C/R122C mice showed a dramatic increase in proliferating stem cells as well as inhibition of differentiation. Tellingly, RUNX3R122C/R122C mice also exhibited a precancerous phenotype. This review focuses on the impact of RUNX3 dysregulation on (1) stem cell fate and (2) the molecular mechanisms underpinning early carcinogenesis.
KW - RUNX3
KW - cancer
KW - cell cycle
KW - differentiation block
KW - early-stage cancer
KW - proliferation
KW - stem cells
UR - http://www.scopus.com/inward/record.url?scp=85147800327&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85147800327&partnerID=8YFLogxK
U2 - 10.3390/cells12030408
DO - 10.3390/cells12030408
M3 - Review article
C2 - 36766749
AN - SCOPUS:85147800327
SN - 2073-4409
VL - 12
JO - Cells
JF - Cells
IS - 3
M1 - 408
ER -
