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Although aerobic glycolysis (the Warburg effect) is a hallmark of cancer, key questions, including when, how, and why cancer cells become highly glycolytic, remain less clear. For a largely unknown regulatory mechanism, a rate-limiting glycolytic enzyme pyruvate kinase M2 (PKM2) isoform is exclusively expressed in embryonic, proliferating, and tumor cells, and plays an essential role in tumor metabolism and growth. Because the receptor tyrosine kinase/PI3K/AKT/mammalian target of rapamycin (RTK/PI3K/AKT/mTOR) signaling cascade is a frequently altered pathway in cancer, we explored its potential role in cancer metabolism. We identified mTOR as a central activator of the Warburg effect by inducing PKM2 and other glycolytic enzymes under normoxic conditions. PKM2 level was augmented in mouse kidney tumors due to deficiency of tuberous sclerosis complex 2 and consequent mTOR activation, and was reduced in human cancer cells by mTOR suppression. mTOR up-regulation of PKM2 expression was through hypoxia-inducible factor 1α (HIF1α)-mediated transcription activation, and c-Myc-heterogeneous nuclear ribonucleoproteins (hnRNPs)-dependent regulation of PKM2 gene splicing. Disruption of PKM2 suppressed oncogenic mTOR-mediated tumorigenesis. Unlike normal cells, mTOR hyperactive cells were more sensitive to inhibition of mTOR or glycolysis. Dual suppression of mTOR and glycolysis synergistically blunted the proliferation and tumor development of mTOR hyperactive cells. Even though aerobic glycolysis is not required for breach of senescence for immortalization and transformation, the frequently deregulated mTOR signaling during multistep oncogenic processes could contribute to the development of the Warburg effect in many cancers. Components of the mTOR/HIF1α/Myc-hnRNPs/PKM2 glycolysis signaling network could be targeted for the treatment of cancer caused by an aberrant RTK/PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

A novel transcription factor, TcAP2, was isolated from Taxus cuspidata by yeast one-hybrid strategy. This factor interacts with jasmonate- and elicitor-responsive element. Analysis of the deduced TcAP2 amino acid sequence revealed that TcAP2 contained a conserved AP2/ethylene-responsive element binding protein domain that consisted of 268 amino acids in a potential nuclear localization sequence. The factor of TcAP2 had a high homology, in its AP2 domain, to other AP2 family members. Based on phylogenetic analysis, it was different from other five DRE-binding proteins in their evolutionary relationship. The transcription of TcAP2 gene in yew accumulated primarily in young organs, such as young stems. Quantitative real-time RT-PCR analysis indicated that TcAP2 gene was inducible to express by treatments with methyl jasmonate plus salicylic acid, high salinity, and cold. This gene showed no response to either abscisic acid or drought treatment. [ABSTRACT FROM AUTHOR]