Abstract:  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 APCmin/+ mice attenuates spontaneous colon cancer formation in APCmin/+ 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.

Source: https://life.xmu.edu.cn/lifeen/2020/0331/c8819a398457/page.htm

Link:  https://www.sciencedirect.com/science/article/pii/S221112472030303X?via%3Dihub