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Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma

Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and...

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Autores principales: Levin, Solomon N., Tomasini, Michael D., Knox, James, Shirani, Mahsa, Shebl, Bassem, Requena, David, Clark, Jackson, Heissel, Søren, Alwaseem, Hanan, Surjan, Rodrigo, Lahasky, Ron, Molina, Henrik, Torbenson, Michael S., Lyons, Barbara, Migler, Rachael D., Coffino, Philip, Simon, Sanford M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284549/
https://www.ncbi.nlm.nih.gov/pubmed/37343102
http://dx.doi.org/10.1126/sciadv.adg7038
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author Levin, Solomon N.
Tomasini, Michael D.
Knox, James
Shirani, Mahsa
Shebl, Bassem
Requena, David
Clark, Jackson
Heissel, Søren
Alwaseem, Hanan
Surjan, Rodrigo
Lahasky, Ron
Molina, Henrik
Torbenson, Michael S.
Lyons, Barbara
Migler, Rachael D.
Coffino, Philip
Simon, Sanford M.
author_facet Levin, Solomon N.
Tomasini, Michael D.
Knox, James
Shirani, Mahsa
Shebl, Bassem
Requena, David
Clark, Jackson
Heissel, Søren
Alwaseem, Hanan
Surjan, Rodrigo
Lahasky, Ron
Molina, Henrik
Torbenson, Michael S.
Lyons, Barbara
Migler, Rachael D.
Coffino, Philip
Simon, Sanford M.
author_sort Levin, Solomon N.
collection PubMed
description Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and pathological alterations in FLC cells, including their drug sensitivity and glycolysis. Hyperammonemic encephalopathy is a recurrent problem in these patients, and established treatments based on the assumption of liver failure are unsuccessful. We show that many of the enzymes that produce ammonia are increased and those that consume ammonia are decreased. We also demonstrate that the metabolites of these enzymes change as expected. Thus, hyperammonemic encephalopathy in FLC may require alternative therapeutics.
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spelling pubmed-102845492023-06-22 Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma Levin, Solomon N. Tomasini, Michael D. Knox, James Shirani, Mahsa Shebl, Bassem Requena, David Clark, Jackson Heissel, Søren Alwaseem, Hanan Surjan, Rodrigo Lahasky, Ron Molina, Henrik Torbenson, Michael S. Lyons, Barbara Migler, Rachael D. Coffino, Philip Simon, Sanford M. Sci Adv Biomedicine and Life Sciences Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and pathological alterations in FLC cells, including their drug sensitivity and glycolysis. Hyperammonemic encephalopathy is a recurrent problem in these patients, and established treatments based on the assumption of liver failure are unsuccessful. We show that many of the enzymes that produce ammonia are increased and those that consume ammonia are decreased. We also demonstrate that the metabolites of these enzymes change as expected. Thus, hyperammonemic encephalopathy in FLC may require alternative therapeutics. American Association for the Advancement of Science 2023-06-21 /pmc/articles/PMC10284549/ /pubmed/37343102 http://dx.doi.org/10.1126/sciadv.adg7038 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Levin, Solomon N.
Tomasini, Michael D.
Knox, James
Shirani, Mahsa
Shebl, Bassem
Requena, David
Clark, Jackson
Heissel, Søren
Alwaseem, Hanan
Surjan, Rodrigo
Lahasky, Ron
Molina, Henrik
Torbenson, Michael S.
Lyons, Barbara
Migler, Rachael D.
Coffino, Philip
Simon, Sanford M.
Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma
title Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma
title_full Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma
title_fullStr Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma
title_full_unstemmed Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma
title_short Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma
title_sort disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284549/
https://www.ncbi.nlm.nih.gov/pubmed/37343102
http://dx.doi.org/10.1126/sciadv.adg7038
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