Abstract 4453: Identification and characterization of oncogenic kinase LASK2 as a diagnostic and therapeutic target for lung cancer

Abstract

Abstract Lung cancer is the leading cause of cancer deaths worldwide. Since the number of patients responding well to standard therapies is still limited, further development of new anti-cancer agents with minimum risk of adverse event is urgently awaited. To screen oncoantigens which could be used for the development of new diagnostic biomarkers and molecular targeted drugs, we have established a screening system as follows; i) To identify overexpressed genes in 120 lung cancers by genome-wide screening using the microarray representing 27,648 genes and pure populations of tumor cells taken from cancer tissues by laser microdissection, ii) To verify the genes for their very low or absent expression in normal tissues by northern-blotting, iii) To validate the clinicopathological significance of their expression with tissue microarray covering hundreds of archived lung cancers, iv) To verify whether the target genes are essential for the growth or survival of lung cancer cells by RNAi and cell growth assays. During this process, we selected dozens of druggable oncogenes with various enzymatic activities, and identified overexpression of protein kinase LASK2 (lung cancer-associated kinase 2) in the majority of lung cancers, but not in normal tissues except testis. Immunocytochemical analysis found LASK2 to be mainly localized in the cytoplasm and nucleus of lung cancer cells. Immunohistochemical analysis revealed that strong LASK2 expression was an independent prognostic factor for non-small cell lung cancer (NSCLC) (P<0.0001). Suppression of LASK2 expression with its specific siRNAs caused growth inhibition of lung cancer cells. The enhanced cellular proliferation by introduction of LASK2 in mammalian cells also supported its oncogenic function. Since LASK2 plays a significant role in the cell proliferation and malignant nature of lung cancers, LASK2 is likely to be a prognostic biomarker and a potential therapeutic target for developing new anti-cancer drugs. Citation Format: Yataro Daigo, Atsushi Takano, Yusuke Nakamura. Identification and characterization of oncogenic kinase LASK2 as a diagnostic and therapeutic target for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4453. doi:10.1158/1538-7445.AM2017-4453