Abstract 391: Serine/threonine kinase LASK2 as a biomarker and therapeutic target for lung cancer

Abstract

Abstract Since the number of lung cancer patients responding well to standard chemotherapies is still small, further development of new anti-cancer drugs with minimum risk of adverse effects and highly sensitive cancer biomarkers for precision medicine is eagerly required. We have been developing new molecular therapies targeting oncogenic proteins with their companion diagnostics by screening system as follows; i) To identify overexpressed genes in 120 lung cancers by our original gene expression profile database, ii) To confirm 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 detected higher expression of serine/threonine kinase LASK2 (lung cancer-associated kinase 2) in the majority of various types of lung cancers, but scarce expression in normal tissues except testis. We further observed much higher expression patterns of LASK2 in brain metastasis as well as advanced primary lung tumors, compared to those in earlier-stage primary lung tumors. Immunohistochemical analysis using tissue microarray showed that strong LASK2 positivity was an independent prognostic factor for NSCLC (P<0.0001). Suppression of LASK2 expression with its siRNAs inhibited growth of lung cancer cells, whereas enhanced cellular proliferation by exogenous expression of LASK2 in mammalian cells also supported its oncogenic function in vitro and in mice model. Invasion of mammalian cells transfected with LASK2-expression vector through Matrigel was significantly enhanced, compared to the control cells transfected with mock or LASK2-kinase dead vector, suggesting that LASK2 could also contribute to the highly malignant phenotype of lung-cancer cells. Induction of LASK2 appeared to activate oncogenic signals for lung cancer such as phosphorylation of MAPK and PCNA. Our data indicate that LASK2 is a promising diagnostic biomarker and therapeutic target for developing precision medicine of lung cancer. Note: This abstract was not presented at the meeting. Citation Format: Yataro Daigo, Atsushi Takano, Yusuke Nakamura. 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 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 391.