title: In vivo genetic dissection of tumor growth and the Warburg effect.
abstract: A well-characterized metabolic landmark for aggressive cancers is the reprogramming from oxidative phosphorylation to aerobic glycolysis, referred to as the Warburg effect. Models mimicking this process are often incomplete due to genetic complexities of tumors and cell lines containing unmapped collaborating mutations. In order to establish a system where individual components of oncogenic signals and metabolic pathways can be readily elucidated, we induced a glycolytic tumor in the Drosophila wing imaginal disc by activating the oncogene PDGF/VEGF-receptor (Pvr). This causes activation of multiple oncogenic pathways including Ras, PI3K/Akt, Raf/ERK, Src and JNK. Together this network of genes stabilizes Hifα (Sima) that in turn, transcriptionally up-regulates many genes encoding glycolytic enzymes. Collectively, this network of genes also causes inhibition of pyruvate dehydrogenase (PDH) activity resulting in diminished ox-phos levels. The high ROS produced during this process functions as a feedback signal to consolidate this metabolic reprogramming.
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors: Cheng-Wei
authors: CW
authors: Wang
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors: Arunima
authors: A
authors: Purkayastha
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors: Kevin T
authors: KT
authors: Jones
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
authors: Shivani K
authors: SK
authors: Thaker
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.|Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States.|Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States.|Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, United States.
authors: Utpal
authors: 0000-0001-6247-0284
authors: U
authors: Banerjee
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004195:Disease Models, Animal; D004330:Drosophila; D029721:Drosophila Proteins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006019:Glycolysis; D009369:Neoplasms / Q000378:metabolism* / Q000503:physiopathology*; D010085:Oxidative Phosphorylation; D011768:Pyruvate Dehydrogenase Complex / Q000096:biosynthesis
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D011768:Pyruvate Dehydrogenase Complex; C100429:Sima protein, Drosophila
keywords: D. melanogaster; LDH; Pvr; cancer; cell biology; developmental biology; hypoxia-inducible factor; metabolism; stem cells; warburg effect