PLEK2 activates the PI3K/AKT signaling pathway to drive lung adenocarcinoma progression by upregulating SPC25.

Abstract

Lung adenocarcinoma (LUAD) is the most common subtype of NSCLC, characterized by poor prognosis and frequently diagnosed at advanced. While previous studies have demonstrated pleckstrin-2 (PLEK2) as aberrantly expressed and implicated in tumorigenesis across various tumor types, including LUAD, the molecular mechanisms underlying PLEK2-mediated LUAD progression remain incompletely understood. In this study, we obtained data from The Cancer Genome Atlas (TCGA) database to assess PLEK2 expression in LUAD, a finding further confirmed through analysis of human tissue specimens. PLEK2-silenced LUAD cellular models were subsequently constructed to examine the functional role of PLEK2 both in vitro and in vivo. Our results showed elevated PLEK2 expression in LUAD, correlating with poor patients'prognosis. PLEK2 knockdown led to a significant suppression of LUAD cell proliferation and migration, accompanied by enhanced apoptosis. Moreover, tumor growth in mice injected with PLEK2-silencing LUAD cells was impaired. Gene expression profiling and Co-IP assays suggested direct interaction between PLEK2 and SPC25, with downregulation of SPC25 similarly impairing cell proliferation and migration. Additionally, we revealed phosphoinositide 3-kinase (PI3K)/AKT signaling activation as requisite for PLEK2-induced malignant phenotypes in LUAD. Collectively, our findings underscore PLEK2's oncogenic potential in LUAD, suggesting its utility as a prognostic indicator and therapeutic target for LUAD management.