Effect of DJ-1 overexpression on the proliferation, apoptosis, invasion and migration of laryngeal squamous cell carcinoma SNU-46 cells through PI3K/AKT/mTOR

Abstract

Abstract. The aim of the present study was to explore the effect of DJ-1-mediated PI3K/AKT/mTOR pathway on the proliferation, apoptosis, invasion, migration and other tumor biological characteristics of laryngeal squamous cell SNU-46, through stable transfection and overexpression of the DJ-1 gene. Retrovirus carrying DJ-1 gene was used to stabilize transfected human laryngeal squamous carcinoma SNU-46 cell line, and monoclonal cell line of stably overexpressed DJ-1 protein was screened out by G418. DJ-1 protein expression was determined by western blotting, and changes of p-AKT, p-mTOR and PTEN protein content were detected, followed by the detection of changes in proliferation, apoptosis, invasion, migration and other tumor biological characteristics of laryngeal squamous carcinoma cell line with stably transfected DJ-1 protein overexpression by flow cytometry, CCK-8 method and Transwell. We successfully constructed a laryngeal squamous carcinoma cell line of stably overexpressed DJ-1 protein and termed it SNU-46-DJ-1. After overexpression of DJ-1 protein, the levels of PTEN expression in laryngeal squamous cell SNU-46 decreased and p-AKT and p-mTOR protein expression levels increased. Compared to the untreated SNU-46 cells, the proliferation rate of SNU-46-DJ-1 cells increased (0.834±0.336 vs. 0.676±0.112; p<0.001); invasiveness was enhanced (165.7±13.6 vs. 100.0±17.4; p=0.001), the migration ability was enhanced (207.3±13.1 vs. 175.3±13.3; p=0.036), and the apoptosis rate decreased (3.533±5.167 vs. 16.397±5.447%; p=0.019). The overexpression of DJ-1 protein in laryngeal squamous carcinoma SNU-46 cells can accelerate proliferation rate, increase the invasion and migration capacity, and reduce apoptosis, by activating the PI3K/AKT/ mTOR pathway.

Mechanistic Nanotherapeutic Approach Based on siRNA-Mediated DJ-1 Protein Suppression for Platinum-Resistant Ovarian Cancer

“…revealed that the overexpression of DJ-1 in laryngeal squamous carcinoma cells is correlated with increased expression of phosphorylated Akt (p-Akt) and the high intracellular levels of DJ-1 can accelerate proliferation rate, increase the invasiveness and migration capacity, and reduce apoptosis, by activating the PI3K/Akt/mTOR signaling axis. 52 It has been confirmed that the proliferation rate of DJ-1-overexpressing SNU-46-D1 cells was faster than normal SNU-46 cells. Through the modulation of this signaling axis DJ-1 has also been implicated in tumor growth and progression by upregulating hypoxia-inducible factor-1 (HIF1) protecting the cells against hypoxia induced apoptosis.…”

Protein profiling identifies mTOR pathway modulation and cytostatic effects of Pim kinase inhibitor, AZD1208, in acute myeloid leukemia

“…It is interesting to note that in addition to inhibition of mTOR pathway protein phosphorylation there was also increase in protein DJ-1 (gene PARK7 ) in the two relatively more AZD1208-sensitive cell lines, MOLM-16 and KG-1a. DJ-1 is involved with response to oxidative stress (reviewed in[27]) as well as promoting cancer cell invasion[28–30]. DJ-1 activation may be a survival mechanism against blockade of Pim kinase and/or mTOR pathway signaling.…”

A proteomic analysis of mushroom polysaccharide-treated HepG2 cells

“…To prevent apoptosis, DJ-1 and the Fas death domain-associated protein (Daxx) (gi|48146287) combine in the nucleus, thus preventing Daxx from associating with ASK1 (gi|5174547) and undergoing a translocation from the nucleus to the cytoplasm 36 . The DJ-1 protein negatively regulate the activity of PTEN (gi|4240387) 37 . Therefore, a lower expression of DJ-1 can decrease the phosphorylation of PKB/Akt, whereas a higher expression of DJ-1 can increase the PKB/Akt phosphorylation and cell survival 38 .…”