Overexpression and Selective Anticancer Efficacy of <i>ENO3</i> in <i>STK11</i> 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, <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 specific gene expression markers (<i>ENO3, TTC39C, LGALS3, and MAML2</i>) 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 <i>STK11</i> loss-of-function. Furthermore, the knockdown of ENO3 expression exhibited selective anticancer effect in <i>STK11</i> mutant cells compared with <i>STK11</i> wild type (or recovered) cells. These findings suggest that ENO3 -based targeted therapy might be promising for patients with lung cancer harboring <i>STK11</i> mutations.