Abstract 5517: Antitumor effect of LRIG1, negative regulator of ErbB, in lung cancer harboring mutant-EGFR

Introduction: EGFR is a member of the ErbB family of tyrosine kinase receptors (RTKs) and plays important roles in the pathogenesis of certain human cancers. In non-small cell lung cancer (NSCLC), mutations in EGFR gene are commonly known as oncogenic driver mutation and targeted for treatment. Leucine rich repeat and immunoglobulin-like domain protein-1 (LRIG1) is a cell surface protein and known as a negative regulator of ErbB family. In brain tumor, LRIG1 was reported to downregulate not only wild-type EGFR, but also EGFRvIII, mutant-type EGFR. But there has been no report about the relationship between LRIG1 and EGFR mutation in the kinase domain frequently found in lung cancer. In this study, we investigate the role of LRIG in EGFR mutant lung cancer from the view point of its effect on signal transduction and cell proliferation and invasion. Method: We examined the LRIG1 expression levels in lung cancer cell lines and the surgically resected primary lung cancer tissues by quantitative PCR assay. We made stable clone of EGFR-mutant cell line (HCC827; exon19del E746-A750) overexpressing GFP tagged LRIG1, and compared with stable clone overexpressing GFP alone. Results: The LRIG1 expression levels in lung cancer cell lines and the surgically resected primary lung cancer tissues were much lower than that in normal bronchial epithelial cells and their normal tissues, respectively. The introduction of LRIG1 decreased EGFR expression and their phosphorylation in EGFR-mutant cell line. LRIG1 strongly suppressed cell proliferation, invasion and migration of EGFR-mutant cell line. In addition, a phospho-RTK array revealed that LRIG1 also downregulated the other RTKs, such as HER2, HER3, MET, and IGF-1R. Conclusion: Our findings demonstrates that LRIG1 decreases the expression and phosphorylation of mutant-EGFR protein and has strong anti-tumor effect in lung cancer harboring EGFR mutation. These findings suggest the importance of LRIG1 related studies to develop a novel strategy for EGFR mutant cancers. Citation Format: Hidejiro Torigoe, Shinichi Toyooka, Masakiyo Sakaguchi, Kazuhiko Shien, Hiromasa Yamamoto, Junichi Soh, Hiroaki Asano, Shuta Tomida, Kazunori Tsukuda, Shinichiro Miyoshi. Antitumor effect of LRIG1, negative regulator of ErbB, in lung cancer harboring mutant-EGFR [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 5517. doi:10.1158/1538-7445.AM2017-5517