Growth factor signaling permits hypoxia-induced autophagy by a HIF1alpha-dependent, BNIP3/3L-independent transcriptional program in human cancer cells.
Several recent reports have demonstrated that autophagy is induced in response to hypoxia in cultured cells. However, the mechanism and consequence of hypoxia-induced autophagy remains unclear as there is no consensus between these studies. In our recent report we show that, in human cancer cells, hypoxia cooperates with growth factor signaling to facilitate a HIF1alpha-driven transcriptional response that promotes autophagy. Here we summarize these findings and set them in context of the findings of other groups, concluding that there are likely multiple routes to different forms of autophagy that serve different purposes downstream of hypoxia, depending upon the degree of stress and cellular context.
Wilkinson
Simon
S
Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Glasgow, UK.
Ryan
Kevin M
KM
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015687:Cell Hypoxia; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C090121:BNIP3 protein, human; C116838:BNIP3L protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins