CHD4 Promotes Breast Cancer Progression as a Coactivator of Hypoxia-Inducible Factors.

Cancer Research
Yijie WangWeibo Luo

Abstract

Recruitment of RNA polymerase II to hypoxia-inducible factor (HIF) target genes under normoxia is a prerequisite for HIF-mediated transactivation. However, the underlying mechanism of this recruitment remains unknown. Here we report that chromodomain helicase DNA-binding protein 4 (CHD4) physically interacts with α and β subunits of HIF1 and HIF2 and enhances HIF-driven transcriptional programs to promote breast cancer progression. Loss of HIF1/2α abolished CHD4-mediated breast tumor growth in mice. In breast cancer cells under normoxia, CHD4 enrichment at HIF target gene promoters increased RNA polymerase II loading through p300. Hypoxia further promoted CHD4 binding to the chromatin via HIF1/2α, where CHD4 in turn enhanced recruitment of HIF1α, leading to HIF target gene transcription. CHD4 was upregulated and correlated with HIF target gene expression in human breast tumors; upregulation of CHD4 and other known HIF coactivators in human breast tumors was mutually exclusive. Furthermore, CHD4 was associated with poor overall survival of patients with breast cancer. Collectively, these findings reveal a new fundamental mechanism of HIF regulation in breast cancer, which has clinical relevance. SIGNIFICANCE: This study identifi...Continue Reading

References

Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·Z AranyD M Livingston
Apr 6, 2004·Methods in Enzymology·Peter VaupelMichael Höckel
Jul 29, 2004·The Journal of Biological Chemistry·Hiroyuki KatoFutoshi Shibasaki
May 24, 2008·Molecular Cell·William G Kaelin, Peter J Ratcliffe
Jul 25, 2009·The Biochemical Journal·Catherine A MusselmanTatiana G Kutateladze
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jason S LeeSung Hee Baek
Nov 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Weibo LuoGregg L Semenza
Jun 12, 2013·Cell·Matthew D GalbraithJoaquín M Espinosa
May 29, 2016·The Journal of Biological Chemistry·Jason K K LowJoel P Mackay
Nov 2, 2016·The Journal of Clinical Investigation·Maria BöhmBeat W Schäfer
Oct 17, 2017·Cellular and Molecular Life Sciences : CMLS·Weibo Luo, Yingfei Wang
Oct 24, 2017·Molecular Cell·Ann BoijaMattias Mannervik
Apr 10, 2018·The Journal of Clinical Investigation·Yan ChenWeibo Luo
Jun 13, 2018·Proceedings of the National Academy of Sciences of the United States of America·Caralynn M WilczewskiFrank L Conlon
Mar 16, 2019·Scientific Reports·Lisa D McKenzieMilan G Chheda
May 16, 2019·Proceedings of the National Academy of Sciences of the United States of America·Tessa ArendsJames R Hagman
Jun 16, 2019·Advances in Experimental Medicine and Biology·Weibo Luo, Yingfei Wang

❮ Previous
Next ❯

Citations

Nov 5, 2020·Briefings in Bioinformatics·Xin ShaoXiaohui Fan
May 14, 2021·Frontiers in Oncology·Apolonia NovilloPablo Gómez-Del Arco
Sep 25, 2021·Environmental Science and Pollution Research International·Fei WuQing Wang

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.