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org.clulab.demo.bio.inactive.PMC-3225393-03-Discussion-01.txt Maven / Gradle / Ivy

MUC1-C oncoprotein promotes glycolysis
Most cancer cells are dependent on aerobic glycolysis for the generation of energy that is needed for cellular processes. This altered metabolism, known as the Warburg effect, involves increased uptake of glucose with decreased utilization of the TCA cycle, such that pyruvate generated during glycolysis is converted to lactate [22]. This metabolic switch, which generates intermediates for cell growth, is induced by certain oncogenes [23]. The present studies demonstrate that transformation of rat 3Y1 fibroblasts with the MUC1-C oncoprotein is associated with increased uptake of glucose and production of lactate. Moreover, silencing of MUC1-C in human breast cancer cells resulted in decreased glucose uptake and lactate production, indicating that MUC1-C contributes to aerobic glycolysis. Activation of the PI3K->Akt pathway has been linked to glucose metabolism through glucose transporter expression, and stimulation of hexokinase and phosphofructokinase activities [24]. In that sense, MUC1-C activates the PI3K->Akt pathway, at least in part, through direct binding of PI3K to a consensus pYHPM motif in the MUC1-C cytoplasmic domain [18], [19]. Thus, MUC1-C could promote aerobic glycolysis through activation of PI3K->Akt signaling. Indeed, silencing Akt in 3Y1/MUC1-CD cells was associated with decreased glucose uptake and partial suppression of lactate production, indicating that MUC1-CD may regulate aerobic glycolysis by Akt-dependent and -independent mechanisms. The present studies provide another link between MUC1-C and aerobic glycolysis through interactions with PKM2. The PKM2 isoform is necessary for conferring the Warburg effect and enables cancer cells to divert glucose metabolites for the synthesis of macromolecules in the response to growth factor stimulation [4], [6], [22]. In this capacity, the regulation of PKM2 is of importance to the metabolism of cancer cells and their ability to form tumors [6]. However, little is known about proteins that interact with PKM2 and affect its activity.