| First Author | Ma H | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 12 | Pages | 4235-4249.e6 |
| PubMed ID | 32209481 | Mgi Jnum | J:288280 |
| Mgi Id | MGI:6416729 | Doi | 10.1016/j.celrep.2020.03.005 |
| Citation | Ma H, et al. (2020) c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3. Cell Rep 30(12):4235-4249.e6 |
| abstractText | Reprogramming of glucose metabolism is a key event in tumorigenesis and progression. Here, we show that active c-Src stimulates glycolysis by phosphorylating (Tyr194) and activating PFKFB3, a key enzyme that boosts glycolysis by producing fructose-2,6-bisphosphate and activating PFK1. Increased glycolysis intermediates replenish non-oxidative pentose phosphate pathway (PPP) and serine pathway for biosynthesis of cancer cells. PFKFB3 knockout (KO) cells and their counterpart reconstituted with PFKFB3-Y194F show comparably impaired abilities for proliferation, migration, and xenograft formation. Furthermore, PFKFB3-Y194F knockin mice show impaired glycolysis and, mating of these mice with APC(min/+) mice attenuates spontaneous colon cancer formation in APC(min/+) mice. In summary, we identify a specific mechanism by which c-Src mediates glucose metabolism to meet cancer cells' requirements for maximal biosynthesis and proliferation. The PFKFB3-Tyr194 phosphorylation level highly correlates with c-Src activity in clinical tumor samples, indicating its potential as an evaluation for tumor prognosis. |
