Abstract 544: Characterization of serine/threonine kinase LASK2 as a biomarker and therapeutic target for lung cancer

Abstract

Abstract As the number of lung cancer patients responding well to standard therapies is still small, further development of new anti-cancer drugs with minimum risk of adverse event and highly sensitive cancer biomarkers is urgently awaited. We have been developing new molecular therapies targeting oncoproteins with their companion biomarkers by screening system as follows; i) To identify up-regulated genes in 120 lung cancers by the gene expression microarray representing 27,648 genes, ii) To verify the candidate genes for their low expression in 23 normal tissues, iii) To validate the clinicopathological significance of their protein expression by tissue microarray covering hundreds of non-small cell lung cancers (NSCLCs), iv) To verify whether they are essential for the growth/invasion of cancer cells by siRNAs. During this process, we selected dozens of druggable oncoproteins with various enzymatic activities, and identified activation of serine/threonine kinase LASK2 (lung cancer-associated kinase 2) in the majority of various histological types of lung cancers, but not in normal tissues except testis. Immunohistochemical analysis showed that strong LASK2 positivity was an independent prognostic factor for patients with NSCLC (P<0.0001). Suppression of LASK2 expression with its siRNAs inhibited growth of lung cancer cells. The enhanced cellular proliferation by introduction of LASK2 in mammalian cells also supported its oncogenic function in vitro and in mice model. Induction of LASK2 appeared to increase the levels of phosphorylation of oncogenic signal proteins for lung cancer such as MAPK. The data suggest that LASK2 is a candidate prognostic biomarker and possible therapeutic target for lung cancers. Citation Format: Yataro Daigo, Atsushi Takano, Yusuke Nakamura. Characterization of serine/threonine kinase LASK2 as a biomarker and therapeutic target for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 544.