Hypoxia-inducible factor-1alpha blocks differentiation of malignant gliomas

The FEBS Journal
Huimin LuGuangmei Yan

Abstract

Aberrant differentiation is a characteristic feature of neoplastic transformation, while hypoxia in solid tumors is believed to be linked to aggressive behavior and poor prognosis. However, the possible relationship between hypoxia and differentiation in malignancies remains poorly defined. Here we show that rat C6 and primary human malignant glioma cells can be induced to differentiate into astrocytes by the well-known adenylate cyclase activator forskolin. However, hypoxia-inducible factor-1alpha expression stimulated by the hypoxia mimetics cobalt chloride or deferoxamine blocks this differentiation and this effectiveness is reversible upon withdrawal of the hypoxia mimetics. Importantly, knockdown of hypoxia inducible factor-1alpha by RNA interference restores the differentiation capabilities of the cells, even in the presence of cobalt chloride, whereas stabilization of hypoxia-inducible factor-1alpha through retarded ubiquitination by von Hippel-Lindau tumor suppressor gene silence abrogates the induced differentiation. Moreover, targeting of HIF-1 using chetomin, a disrupter of HIF-1 binding to its transcriptional co-activator CREB-binding protein (CBP)/p300, abolishes the differentiation-inhibitory effect of hypoxia-ind...Continue Reading

References

May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·G L Wang, G L Semenza
Jan 1, 1997·Pharmacology & Therapeutics·R E Scott
Feb 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·A E HorvaiC K Glass
Nov 21, 1998·The Journal of Biological Chemistry·K FrønsdalF Saatcioglu
Jan 16, 1999·Brain Research. Molecular Brain Research·G A BadrF Ismail-Beigi
Oct 6, 2000·The Journal of Biological Chemistry·L W Yuan, J E Gambee
Jan 11, 2001·The New England Journal of Medicine·L M DeAngelis
Jun 8, 2001·Genes & Development·E A MaherR A DePinho
Oct 2, 2001·Pharmacology & Therapeutics·M LeszczynieckaP B Fisher
Oct 13, 2001·Science·R K Bruick, S L McKnight
Nov 24, 2001·Respiration Physiology·M Erecińska, I A Silver
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Luca RozGabriella Sozzi
Mar 21, 2002·Nature Reviews. Cancer·Adrian L Harris
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Annika JögiSven Påhlman
Sep 6, 2002·Biochemical Pharmacology·Gregg Semenza
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Jan 24, 2004·Journal of Natural Products·Haruhiro FujimotoMasami Ishibashi
Feb 3, 2004·The Journal of Biological Chemistry·Hiromi TakanagaManabu Kunimoto
Apr 9, 2004·The EMBO Journal·Minori KoshijiL Eric Huang
Jun 23, 2004·Critical Reviews in Oncology/hematology·Stewart Sell
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Jun 23, 2005·Cancer Biology & Therapy·Tarek H El-MetwallyThomas E Adrian
Aug 16, 2005·Cancer Cell·Benjamin J MoellerMark W Dewhirst
Nov 1, 2005·Developmental Cell·Maria V GustafssonMaria Bondesson
Dec 21, 2005·Reproduction, Fertility, and Development·Francesca GrasselliFederico Bianco
May 26, 2006·Nature·Jacques PouysségurNathalie M Mazure
Jun 20, 2006·Journal of Neuropathology and Experimental Neurology·Yuan RongDaniel J Brat
Mar 30, 2007·Radiation Research·Anna S E LjungkvistAlbert J van der Kogel
Apr 4, 2007·Cell Cycle·Simone Fulda, Klaus-Michael Debatin
Aug 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yan LiGuangmei Yan

❮ Previous
Next ❯

Citations

Dec 17, 2009·Acta Neuropathologica·Manuel B Graeber, Wolfgang J Streit
Mar 29, 2012·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·S H ShenZ X Wang
Mar 4, 2011·Cell Death & Disease·I GucciniF Malisan
Oct 23, 2012·Journal of Neurosurgery. Pediatrics·Eric M ThompsonEdward A Neuwelt
Feb 11, 2015·Oncogene·A FarriaS Y R Dent
Sep 7, 2016·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Andrew J Ghio
Dec 8, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jason W Locasale, Benjamin J Zeskind
Dec 13, 2016·International Journal of Pharmaceutics·Carla Garcia-MazasMarcos Garcia-Fuentes
Nov 9, 2010·Brain Pathology·Eli E Bar
Aug 14, 2010·Biochemical Pharmacology·Francesca PistollatoGiuseppe Basso
Apr 29, 2021·Neuropsychiatric Disease and Treatment·Ruijie GengXiao Huang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.