Downregulation of Rab17 promotes cell proliferation and invasion in non-small cell lung cancer through STAT3/HIF-1α/VEGF signaling

Background Rab GTPases play a key role in regulating intercellular vesicle trafficking in both exo- and endocytic pathways. Recent studies have reported that Rab small GTPases and the associated regulatory proteins and effectors are involved in many cancers. The purpose of this study was to investigate the biological role of Rab17 in non-small cell lung cancer (NSCLC) and the relative mechanism. Methods Rab17 expression in human NSCLC cell lines and tissues was evaluated using real-time PCR (RT-PCR), western blot and immunohistochemical (IHC) staining. NSCLC cell lines with RAB17 stable knockdown were generated to explore its function in vitro and in vivo. Additionally, we investigated the potential mechanism of Rab17 by identifying the expression levels of STAT3/HIF-1 alpha/VEGF pathway using western blot analysis. Results Decreased Rab17 expression was correlated with poor overall survival in NSCLC patients. The functional assays showed that knockdown of Rab17 could promote tumorigenic properties of NSCLC cells in vitro and in vivo, including enhanced cell proliferation, colony formation, invasion and migration, angiogenesis and tumor xenograft growth, and suppressed apoptosis. Moreover, Rab17 downregulation decreased epithelial marker E-cadherin and increased mesenchymal markers Vimentin and beta-catenin, suggesting knockdown of Rab17 induced epithelial-mesenchymal transition (EMT). Conclusion Downregulation of Rab17 promotes cell invasion and enhances tumorigenicity in part through the STAT3/HIF-1 alpha/VEGF pathway, which may represent a novel potential therapeutic target.