Mer receptor tyrosine kinase is frequently overexpressed in human non-small cell lung cancer, confir

• 作 者: Shengzhi Xie Yongwu Li Xiaoyan Li Linxiong Wang Na Yang Yadi Wang Huafeng Wei
• 机 构: International Joint Cancer Institute,Second Military Medical University,Shanghai,China;Department of
• 出 处: 2015年北京放射肿瘤年会
• 发表日期: 2016年5期
• 关键词: mer receptor tyrosine kinase NSCLC targeted therapy erlotinib resistance

　　Mer is a receptor tyrosine kinase (RTK) with oncogenic properties that is often overexpressed or activated in various malignancies.Using both immunohistochemistry and microarray analyses, we demonstrated that Mer was overexpressed in both tumoral and stromal compartments of about 70% of non-small cell lung cancer (NSCLC) samples relative to surrounding normal lung tissue.This was validated in freshly harvested NSCLC samples;however, no associations were found between Mer expression and patient features.Although Mer overexpression did not render normal lung epithelial cell tumorigenic in vivo, it promoted the in vitro cell proliferation,clonogenic colony formation and migration of normal lung epithelial cells as well as NSCLC cells primarily depending on MAPK and FAK signaling, respectively.Importantly, Mer overexpression induced resistance to erlotinib (EGFR inhibitor) in otherwise erlotinib-sensitive cells.Furthermore, Mer-specific inhibitor rendered erlotinib-resistant cells sensitive to erlotinib.We conclude that Mer enhances malignant phenotype and pharmacological inhibition of Mer overcomes resistance of NSCLC to EGFR-targeted agents.