PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation

• DOI: 10.1186/s12943-015-0490-2
• Publication Date: 2016-01-06T12:53:34Z
• Authors: Ninel Azoitei; Alexander Becher; Konrad Steinestel; Arefeh Rouhi; Kristina Diepold; Felicitas Genze; Thomas Simmet; Thomas Seufferlein
• Keywords: PKM2

Initially identified as a molecule that regulates the final step of glycolysis, M2 isoform pyruvate kinase (PKM2) was recently reported to have central role in metabolic reprogramming cancer cells well participating cell cycle progression and gene transcription. Despite intensive efforts, intricate molecular mechanisms through which PKM2 tumor remain elusive.The proliferation apoptosis various pancreatic using lentiviral-mediated abrogation were assessed vitro via Western blot flow cytometric assay while vivo experiments involved xenograft on chicken chorionallantoic membranes immunohistochemistry human tissue specimens. In order decipher mechanism HIF-1α p65/RelA regulation by cultivated hypoxic atmosphere or normoxia we biochemical assays such blotting, immunoprecipitation, reporter ELISA.Strong expression observed 68 % adenocarcinoma specimens almost all analyzed lines. Abrogation resulted impaired augmented growth decreased blood vessel formation vivo. Furthermore, deletion negatively impacted hypoxia-induced accumulation promoter activity ultimately resulting secretion VEGF.Our study suggests tumors interferes both with NF-κB/p65 activation triggers VEGF-A subsequent formation.