A Macrophage-Dominant PI3K Isoform Controls Hypoxia-Induced HIF1α and HIF2α Stability and Tumor Growth, Angiogenesis, and Metastasis

• Published in: Molecular cancer research Vol. 12; no. 10; pp. 1520 - 1531
• Main Authors: Joshi, Shweta, Singh, Alok R., Zulcic, Muamera, Durden, Donald L.
• Format: Journal Article
• Language: English
• Published: United States 01.10.2014
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cell Hypoxia - drug effects; Cell Proliferation - drug effects; Chromones - pharmacology; Gene Deletion; Gene Expression Regulation, Neoplastic - drug effects; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Isoenzymes - metabolism; Macrophages - drug effects; Macrophages - enzymology; Mice; Models, Biological; Neoplasm Metastasis; Neoplasms - blood supply; Neoplasms - enzymology; Neoplasms - genetics; Neoplasms - pathology; Neovascularization, Pathologic - enzymology; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Oligopeptides - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Proteasome Endopeptidase Complex - metabolism; Protein Kinase Inhibitors - pharmacology; Protein Stability - drug effects; Proteolysis - drug effects; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Transcription, Genetic - drug effects; Vascular Endothelial Growth Factor A - metabolism

Tumor growth, progression, and response to the hypoxic tumor microenvironment involve the action of hypoxia-inducible transcription factors, HIF1 and HIF2. HIF is a heterodimeric transcription factor containing an inducible HIFα subunit and a constitutively expressed HIFβ subunit. The signaling path...