PLEK2 promotes lung adenocarcinoma progression via activating the PI3K/AKT signaling pathway through SPC25 Running title: PLEK2 promotes LUAD via SPC25/PI3K/AKT axis

Abstract

Abstract Lung adenocarcinoma (LUAD) is the most common form of NSCLC with poor outcomes and late diagnosis. Previous studies have demonstrated the abnormal expression and promoting role of Pleckstrin-2 (PLEK2) in several tumor types including LUAD, the molecular mechanism of PLEK2 to LUAD progression has not been elucidated clearly. In this study, the expression of PLEK2 in LUAD was analyzed using public available the Cancer Genome Atlas (TCGA) database and further confirmed in human tissue specimens. PLEK2-silencing LUAD cell models were subsequently constructed for examining the function of PLEK2 at in vitro and in vivo level. Our results showed that PLEK2 was highly expressed in LUAD, and this high level of expression was correlated with poor patients’ prognosis. PLEK2 knockdown led to a significant suppression of proliferation and migration of LUAD cells, whereas enhanced apoptosis. Moreover, tumor growth in mice injected with PLEK2-silencing LUAD cells was also impaired. The gene-expression profiling and Co-IP assays suggested that PLEK2 could directly interact with SPC25. Downregulation of SPC25 also impaired the cell proliferation and migration abilities. Additionally, we revealed that the activation of phosphoinositide 3-kinase (PI3K)/AKT signaling was required for PLEK2-induced malignant phenotypes of LUAD cells. PLEK2 exerted a promoting role in LUAD, and might be prognostic indicator and therapeutic target for LUAD patient.