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


ABSTRACT: 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-offunction 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.

SUBMITTER: Park C 

PROVIDER: S-EPMC6883975 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Overexpression and Selective Anticancer Efficacy of <i>ENO3</i> in <i>STK11</i> Mutant Lung Cancers.

Park Choa C   Lee Yejin Y   Je Soyeon S   Chang Shengzhi S   Kim Nayoung N   Jeong Euna E   Yoon Sukjoon S  

Molecules and cells 20191101 11


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, <i><i>STK11</i> (LKB1)</i> are important in lung cancer progression, <i><i>STK11</i></i> is not the direct target for anticancer agents. We attempted to identify cancer transcriptome signatures associated with <i>STK11</i> loss-offunction mutations. Several new sensitive and speci  ...[more]

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