Hypoxia and the unfolded protein response.
Tumor hypoxia refers to the development of regions within solid tumors in which the oxygen concentration is lower (0-3%) compared to that in most normal tissues (4-9%) (Vaupel and Hockel, 2000). Considerable experimental and clinical evidence exists supporting the notion that hypoxia fundamentally alters the physiology of the tumor towards a more aggressive phenotype (Hockel and Vaupel, 2001). Therefore, delineating the mechanisms by which hypoxia affects tumor physiology at the cellular and molecular levels will be crucial for a better understanding of tumor development and metastasis and for designing better antitumor modalities.
Koumenis
Constantinos
C
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Bi
Meixia
M
Ye
Jiangbin
J
Feldman
Douglas
D
Koong
Albert C
AC
D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000693:Anaerobiosis; D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000032:analysis*; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism
D051701:Activating Transcription Factor 4; D004268:DNA-Binding Proteins; D004722:Endoribonucleases; D015852:Eukaryotic Initiation Factor-2; D008565:Membrane Proteins; D010100:Oxygen; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D019892:eIF-2 Kinase; C403982:ERN2 protein, human