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HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth

Many anti-cancer therapeutics lead to the release of danger associated pattern molecules (DAMPs) as the result of killing large numbers of both normal and transformed cells as well as lysis of red blood cells (RBC) (hemolysis). Labile heme originating from hemolysis acts as a DAMP while its breakdow...

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Autores principales: Canesin, Giacomo, Muralidharan, Anindhita Meena, Swanson, Kenneth D., Wegiel, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307061/
https://www.ncbi.nlm.nih.gov/pubmed/34359970
http://dx.doi.org/10.3390/cells10071801
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author Canesin, Giacomo
Muralidharan, Anindhita Meena
Swanson, Kenneth D.
Wegiel, Barbara
author_facet Canesin, Giacomo
Muralidharan, Anindhita Meena
Swanson, Kenneth D.
Wegiel, Barbara
author_sort Canesin, Giacomo
collection PubMed
description Many anti-cancer therapeutics lead to the release of danger associated pattern molecules (DAMPs) as the result of killing large numbers of both normal and transformed cells as well as lysis of red blood cells (RBC) (hemolysis). Labile heme originating from hemolysis acts as a DAMP while its breakdown products exert varying immunomodulatory effects. Labile heme is scavenged by hemopexin (Hx) and processed by heme oxygenase-1 (HO-1, Hmox1), resulting in its removal and the generation of biliverdin/bilirubin, carbon monoxide (CO) and iron. We recently demonstrated that labile heme accumulates in cancer cell nuclei in the tumor parenchyma of Hx knockout mice and contributes to the malignant phenotype of prostate cancer (PCa) cells and increased metastases. Additionally, this work identified Hx as a tumor suppressor gene. Direct interaction of heme with DNA G-quadruplexes (G4) leads to altered gene expression in cancer cells that regulate transcription, recombination and replication. Here, we provide new data supporting the nuclear role of HO-1 and heme in modulating DNA damage response, G4 stability and cancer growth. Finally, we discuss an alternative role of labile heme as a nuclear danger signal (NDS) that regulates gene expression and nuclear HO-1 regulated DNA damage responses stimulated by its interaction with G4.
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spelling pubmed-83070612021-07-25 HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth Canesin, Giacomo Muralidharan, Anindhita Meena Swanson, Kenneth D. Wegiel, Barbara Cells Communication Many anti-cancer therapeutics lead to the release of danger associated pattern molecules (DAMPs) as the result of killing large numbers of both normal and transformed cells as well as lysis of red blood cells (RBC) (hemolysis). Labile heme originating from hemolysis acts as a DAMP while its breakdown products exert varying immunomodulatory effects. Labile heme is scavenged by hemopexin (Hx) and processed by heme oxygenase-1 (HO-1, Hmox1), resulting in its removal and the generation of biliverdin/bilirubin, carbon monoxide (CO) and iron. We recently demonstrated that labile heme accumulates in cancer cell nuclei in the tumor parenchyma of Hx knockout mice and contributes to the malignant phenotype of prostate cancer (PCa) cells and increased metastases. Additionally, this work identified Hx as a tumor suppressor gene. Direct interaction of heme with DNA G-quadruplexes (G4) leads to altered gene expression in cancer cells that regulate transcription, recombination and replication. Here, we provide new data supporting the nuclear role of HO-1 and heme in modulating DNA damage response, G4 stability and cancer growth. Finally, we discuss an alternative role of labile heme as a nuclear danger signal (NDS) that regulates gene expression and nuclear HO-1 regulated DNA damage responses stimulated by its interaction with G4. MDPI 2021-07-16 /pmc/articles/PMC8307061/ /pubmed/34359970 http://dx.doi.org/10.3390/cells10071801 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Canesin, Giacomo
Muralidharan, Anindhita Meena
Swanson, Kenneth D.
Wegiel, Barbara
HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth
title HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth
title_full HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth
title_fullStr HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth
title_full_unstemmed HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth
title_short HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth
title_sort ho-1 and heme: g-quadruplex interaction choreograph dna damage responses and cancer growth
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307061/
https://www.ncbi.nlm.nih.gov/pubmed/34359970
http://dx.doi.org/10.3390/cells10071801
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