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Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers

Recent findings in colon cancer cells indicate that inhibition of the mitochondrial H(+)-adenosine triphosphate (ATP) synthase by the ATPase inhibitory factor 1 (IF1) promotes aerobic glycolysis and a reactive oxygen species (ROS)-mediated signal that enhances proliferation and cell survival. Herein...

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Autores principales: Sánchez-Aragó, M, Formentini, L, Martínez-Reyes, I, García-Bermudez, J, Santacatterina, F, Sánchez-Cenizo, L, Willers, I M, Aldea, M, Nájera, L, Juarránz, Á, López, E C, Clofent, J, Navarro, C, Espinosa, E, Cuezva, J M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641363/
https://www.ncbi.nlm.nih.gov/pubmed/23608753
http://dx.doi.org/10.1038/oncsis.2013.9
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author Sánchez-Aragó, M
Formentini, L
Martínez-Reyes, I
García-Bermudez, J
Santacatterina, F
Sánchez-Cenizo, L
Willers, I M
Aldea, M
Nájera, L
Juarránz, Á
López, E C
Clofent, J
Navarro, C
Espinosa, E
Cuezva, J M
author_facet Sánchez-Aragó, M
Formentini, L
Martínez-Reyes, I
García-Bermudez, J
Santacatterina, F
Sánchez-Cenizo, L
Willers, I M
Aldea, M
Nájera, L
Juarránz, Á
López, E C
Clofent, J
Navarro, C
Espinosa, E
Cuezva, J M
author_sort Sánchez-Aragó, M
collection PubMed
description Recent findings in colon cancer cells indicate that inhibition of the mitochondrial H(+)-adenosine triphosphate (ATP) synthase by the ATPase inhibitory factor 1 (IF1) promotes aerobic glycolysis and a reactive oxygen species (ROS)-mediated signal that enhances proliferation and cell survival. Herein, we have studied the expression, biological relevance, mechanism of regulation and potential clinical impact of IF1 in some prevalent human carcinomas. We show that IF1 is highly overexpressed in most (>90%) of the colon (n=64), lung (n=30), breast (n=129) and ovarian (n=10) carcinomas studied as assessed by different approaches in independent cohorts of cancer patients. The expression of IF1 in the corresponding normal tissues is negligible. By contrast, the endometrium, stomach and kidney show high expression of IF1 in the normal tissue revealing subtle differences by carcinogenesis. The overexpression of IF1 also promotes the activation of aerobic glycolysis and a concurrent ROS signal in mitochondria of the lung, breast and ovarian cancer cells mimicking the activity of oligomycin. IF1-mediated ROS signaling activates cell-type specific adaptive responses aimed at preventing death in these cell lines. Remarkably, regulation of IF1 expression in the colon, lung, breast and ovarian carcinomas is exerted at post-transcriptional levels. We demonstrate that IF1 is a short-lived protein (t(1/2) ∼100 min) strongly implicating translation and/or protein stabilization as main drivers of metabolic reprogramming and cell survival in these human cancers. Analysis of tumor expression of IF1 in cohorts of breast and colon cancer patients revealed its relevance as a predictive marker for clinical outcome, emphasizing the high potential of IF1 as therapeutic target.
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spelling pubmed-36413632013-05-02 Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers Sánchez-Aragó, M Formentini, L Martínez-Reyes, I García-Bermudez, J Santacatterina, F Sánchez-Cenizo, L Willers, I M Aldea, M Nájera, L Juarránz, Á López, E C Clofent, J Navarro, C Espinosa, E Cuezva, J M Oncogenesis Original Article Recent findings in colon cancer cells indicate that inhibition of the mitochondrial H(+)-adenosine triphosphate (ATP) synthase by the ATPase inhibitory factor 1 (IF1) promotes aerobic glycolysis and a reactive oxygen species (ROS)-mediated signal that enhances proliferation and cell survival. Herein, we have studied the expression, biological relevance, mechanism of regulation and potential clinical impact of IF1 in some prevalent human carcinomas. We show that IF1 is highly overexpressed in most (>90%) of the colon (n=64), lung (n=30), breast (n=129) and ovarian (n=10) carcinomas studied as assessed by different approaches in independent cohorts of cancer patients. The expression of IF1 in the corresponding normal tissues is negligible. By contrast, the endometrium, stomach and kidney show high expression of IF1 in the normal tissue revealing subtle differences by carcinogenesis. The overexpression of IF1 also promotes the activation of aerobic glycolysis and a concurrent ROS signal in mitochondria of the lung, breast and ovarian cancer cells mimicking the activity of oligomycin. IF1-mediated ROS signaling activates cell-type specific adaptive responses aimed at preventing death in these cell lines. Remarkably, regulation of IF1 expression in the colon, lung, breast and ovarian carcinomas is exerted at post-transcriptional levels. We demonstrate that IF1 is a short-lived protein (t(1/2) ∼100 min) strongly implicating translation and/or protein stabilization as main drivers of metabolic reprogramming and cell survival in these human cancers. Analysis of tumor expression of IF1 in cohorts of breast and colon cancer patients revealed its relevance as a predictive marker for clinical outcome, emphasizing the high potential of IF1 as therapeutic target. Nature Publishing Group 2013-04 2013-04-22 /pmc/articles/PMC3641363/ /pubmed/23608753 http://dx.doi.org/10.1038/oncsis.2013.9 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Sánchez-Aragó, M
Formentini, L
Martínez-Reyes, I
García-Bermudez, J
Santacatterina, F
Sánchez-Cenizo, L
Willers, I M
Aldea, M
Nájera, L
Juarránz, Á
López, E C
Clofent, J
Navarro, C
Espinosa, E
Cuezva, J M
Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers
title Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers
title_full Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers
title_fullStr Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers
title_full_unstemmed Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers
title_short Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers
title_sort expression, regulation and clinical relevance of the atpase inhibitory factor 1 in human cancers
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641363/
https://www.ncbi.nlm.nih.gov/pubmed/23608753
http://dx.doi.org/10.1038/oncsis.2013.9
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