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.

CircAGFG1 drives metastasis and stemness in colorectal cancer by modulating YY1/CTNNB1

“…It has been indicated that YY1 acts as an important transcription factor to affect critical gene expression. For example, YY1 promotes tumorigenesis via regulating glucose transporter GLUT3 27 . YY1 enhances G6PD transcription and directly activates the pentose phosphate pathway to accelerate cell proliferation 28 .…”

Molecular interplay between linc01134 and YY1 dictates hepatocellular carcinoma progression

“…YY1 can function as transcription factor and plays an important regulatory role in various biological processes by binding to DNA and numerous proteins, consequently impacting the pathologic processes of cancers [19][20][21][22]. YY1 has been reported to induce lncRNA MCM3AP-AS1 overexpression in lung cancer, and overexpressed MCM3AP-AS1 promoted angiogenesis via targeting KPNA4 through shared miR-340-5p [23].…”

Flavonoids against the Warburg phenotype—concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism

“…Recent experimental studies have demonstrated its role in the silencing of oxidative phosphorylation and switching to aerobic glycolysis [ 53 ]. Additionally, an oncogenic transcription factor, Yin Yang 1 (YY1), promotes aerobic glycolysis via upregulation of GLUT3 [ 54 ].…”