Yin Yang 1 promotes the Warburg effect and tumorigenesis via glucose transporter GLUT3.

Abstract

Cancer cells typically shift their metabolism to aerobic glycolysis to fulfill the demand of energy and macromolecules to support their proliferation. Glucose transporter (GLUT) family-mediated glucose transport is the pacesetter of aerobic glycolysis and, thus, is critical for tumor cell metabolism. Yin Yang 1 (YY1) is an oncogene crucial for tumorigenesis; however, its role in tumor cell glucose metabolism remains unclear. Here, we revealed that YY1 activates GLUT3 transcription by directly binding to its promoter and, concomitantly, enhances tumor cell aerobic glycolysis. This regulatory effect of YY1 on glucose entry into the cells is critical for YY1-induced tumor cell proliferation and tumorigenesis. Intriguingly, YY1 regulation of GLUT3 expression, and, subsequently, of tumor cell aerobic glycolysis and tumorigenesis, occurs p53-independently. Our results also showed that clinical drug oxaliplatin suppresses colon carcinoma cell proliferation by inhibiting the YY1/GLUT3 axis. Together, these results link YY1's tumorigenic potential with the critical first step of aerobic glycolysis. Thus, our novel findings not only provide new insights into the complex role of YY1 in tumorigenesis but also indicate the potential of YY1 as a target for cancer therapy irrespective of the p53 status.

• Authors: Yali Wang, Shourong Wu, Can Huang, Yanjun Li, Hezhao Zhao, Vivi Kasim
• Journal: Cancer science (Cancer Sci) Vol. 109 Issue 8 Pg. 2423-2434 (Aug 2018) ISSN: 1349-7006 [Electronic] England
• PMID: 29869834 (Publication Type: Journal Article)
• Copyright: © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Glucose Transporter Type 3
• Organoplatinum Compounds
• Tumor Suppressor Protein p53
• YY1 Transcription Factor
• Oxaliplatin

Topics

• Animals
• Carcinogenesis (drug effects, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects, genetics)
• Glucose Transporter Type 3 (genetics)
• Glycolysis (drug effects, genetics)
• HCT116 Cells
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Organoplatinum Compounds (pharmacology)
• Oxaliplatin
• Promoter Regions, Genetic (genetics)
• Tumor Suppressor Protein p53 (genetics)
• Walker-Warburg Syndrome (genetics, pathology)
• YY1 Transcription Factor (genetics)