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Overexpression and Selective Anticancer Efficacy of ENO3 in STK11 Mutant Lung Cancers

Oncogenic gain-of-function mutations are clinical biomarkers for most targeted therapies, as well as represent direct targets for drug treatment. Although loss-of-function mutations involving the tumor suppressor gene, STK11 (LKB1) are important in lung cancer progression, STK11 is not the direct ta...

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Autores principales: Park, Choa, Lee, Yejin, Je, Soyeon, Chang, Shengzhi, Kim, Nayoung, Jeong, Euna, Yoon, Sukjoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883975/
https://www.ncbi.nlm.nih.gov/pubmed/31697874
http://dx.doi.org/10.14348/molcells.2019.0099
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author Park, Choa
Lee, Yejin
Je, Soyeon
Chang, Shengzhi
Kim, Nayoung
Jeong, Euna
Yoon, Sukjoon
author_facet Park, Choa
Lee, Yejin
Je, Soyeon
Chang, Shengzhi
Kim, Nayoung
Jeong, Euna
Yoon, Sukjoon
author_sort Park, Choa
collection PubMed
description Oncogenic gain-of-function mutations are clinical biomarkers for most targeted therapies, as well as represent direct targets for drug treatment. Although loss-of-function mutations involving the tumor suppressor gene, STK11 (LKB1) are important in lung cancer progression, STK11 is not the direct target for anticancer agents. We attempted to identify cancer transcriptome signatures associated with STK11 loss-of-function mutations. Several new sensitive and specific gene expression markers (ENO3, TTC39C, LGALS3, and MAML2) were identified using two orthogonal measures, i.e., fold change and odds ratio analyses of transcriptome data from cell lines and tissue samples. Among the markers identified, the ENO3 gene over-expression was found to be the direct consequence of STK11 loss-of-function. Furthermore, the knockdown of ENO3 expression exhibited selective anticancer effect in STK11 mutant cells compared with STK11 wild type (or recovered) cells. These findings suggest that ENO3-based targeted therapy might be promising for patients with lung cancer harboring STK11 mutations.
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spelling pubmed-68839752019-12-06 Overexpression and Selective Anticancer Efficacy of ENO3 in STK11 Mutant Lung Cancers Park, Choa Lee, Yejin Je, Soyeon Chang, Shengzhi Kim, Nayoung Jeong, Euna Yoon, Sukjoon Mol Cells Articles Oncogenic gain-of-function mutations are clinical biomarkers for most targeted therapies, as well as represent direct targets for drug treatment. Although loss-of-function mutations involving the tumor suppressor gene, STK11 (LKB1) are important in lung cancer progression, STK11 is not the direct target for anticancer agents. We attempted to identify cancer transcriptome signatures associated with STK11 loss-of-function mutations. Several new sensitive and specific gene expression markers (ENO3, TTC39C, LGALS3, and MAML2) were identified using two orthogonal measures, i.e., fold change and odds ratio analyses of transcriptome data from cell lines and tissue samples. Among the markers identified, the ENO3 gene over-expression was found to be the direct consequence of STK11 loss-of-function. Furthermore, the knockdown of ENO3 expression exhibited selective anticancer effect in STK11 mutant cells compared with STK11 wild type (or recovered) cells. These findings suggest that ENO3-based targeted therapy might be promising for patients with lung cancer harboring STK11 mutations. Korean Society for Molecular and Cellular Biology 2019-11 2019-11-07 /pmc/articles/PMC6883975/ /pubmed/31697874 http://dx.doi.org/10.14348/molcells.2019.0099 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.
spellingShingle Articles
Park, Choa
Lee, Yejin
Je, Soyeon
Chang, Shengzhi
Kim, Nayoung
Jeong, Euna
Yoon, Sukjoon
Overexpression and Selective Anticancer Efficacy of ENO3 in STK11 Mutant Lung Cancers
title Overexpression and Selective Anticancer Efficacy of ENO3 in STK11 Mutant Lung Cancers
title_full Overexpression and Selective Anticancer Efficacy of ENO3 in STK11 Mutant Lung Cancers
title_fullStr Overexpression and Selective Anticancer Efficacy of ENO3 in STK11 Mutant Lung Cancers
title_full_unstemmed Overexpression and Selective Anticancer Efficacy of ENO3 in STK11 Mutant Lung Cancers
title_short Overexpression and Selective Anticancer Efficacy of ENO3 in STK11 Mutant Lung Cancers
title_sort overexpression and selective anticancer efficacy of eno3 in stk11 mutant lung cancers
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883975/
https://www.ncbi.nlm.nih.gov/pubmed/31697874
http://dx.doi.org/10.14348/molcells.2019.0099
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