Abstract 1142: STK31 contributes to lung carcinogenesis through induction of stemness and resistance to EGFR-TKI therapy

Lung adenocarcinoma (LUAD), the most common histological subtype of lung cancer, remains one of the leading causes of cancer-related deaths worldwide. With improving knowledge in the molecular aberrations underlying lung carcinogenesis, a large number of targeted therapies are being developed to better patient9s survival. EGFR-activating mutations are one of the most frequent genetic alterations in advanced lung adenocarcinoma, and patients harbouring certain types of EGFR activating mutation confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Despite promising initial responses, majority of patients develop resistance to treatment and the mechanism of resistance remains unknown in up to 30% of patients. Recent studies revealed that cancer stem cells (CSCs) endowed with stem cell-like properties confer resistance to EGFR-TKI treatment. Identification of pathways maintaining stemness properties potentially provide novel drug targets to overcome treatment resistance. Protein phosphorylation is the most common form of reversible post-translational modification and is frequently involved in the deregulation of signal transductions associated with cancer development and progression. In this study, we have identified Serine/Threonine Kinase 31 (STK31) to be upregulated in enriched lung CSC populations, as well as in the erlotinib resistant derivatives from two LUAD cell lines. Through analysing The Cancer Genome Atlas (TCGA) data, mRNA expression of STK31 is observed to be higher in LUAD tumor when compared with paired normal tissues (p Citation Format: Eunice Yuen-Ting Lau, Isabella Kit-Nam Chin, Alvin Hong-Wai Fong, Victor Wan-San Ma, William Chi-Shing Cho. STK31 contributes to lung carcinogenesis through induction of stemness and resistance to EGFR-TKI therapy [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 1142.