FBXO17 promotes cell proliferation through activation of Akt in lung adenocarcinoma cells

作者：Tomeka L. Suber, Ina Nikolli, Michael E. O’Brien, J.D. Londino, Jing Zhao, Kong Chen, Rama K. Mallampalli, Yutong Zhao · 发表于：Respiratory Research · 年份：2018 · DOI：10.1186/s12931-018-0910-0 · 被引用次数：51 · 研究领域：Ubiquitin and proteasome pathways、PI3K/AKT/mTOR signaling in cancer、Microtubule and mitosis dynamics

BACKGROUND: The ubiquitin-proteasome pathway, mediated in part, by ubiquitin E3 ligases, is critical in regulating cellular processes such as cell proliferation, apoptosis, and migration. FBXO17 was recently identified as an F-box protein that targets glycogen synthase kinase-3β to the E3 ubiquitin ligase protein complex for polyubiquitination and proteasomal degradation. Here, we identified that in several lung adenocarcinoma cell lines, FBXO17 cellular protein was detected at relatively high levels, as was expression in a subset of lung cancers. Hence, we investigated the effects of FBXO17 on cell proliferation. METHODS: Single cell RNA sequencing analysis was performed on a resection of a non-small cell lung carcinoma tumor to examine FBXO17 expression. Multiple lung cancer cell lines were immunoblotted, and The Cancer Genome Atlas was analyzed to determine if FBXO17 expression was amplified in a subset of lung cancers. A549 cells were transfected with empty vector or FBXO17-V5 plasmid and immunoblotted for Akt pathway mediators including PDK1, ERK1/2, ribosomal protein S6, and CREB. Cell proliferation and viability were analyzed by trypan blue exclusion, BrdU incorporation and an MTS-based fluorometric assay. Studies were also performed after transfecting with sifbxo17. Samples were used in an RNA microarray analysis to evaluate pathways affected by reduced FBXO17 gene expression. RESULTS: We observed that overexpression of FBXO17 increased A549 cell proliferation coupled...