VEGFA Upregulates FLJ10540 and Modulates Migration and Invasion of Lung Cancer via PI3K/AKT Pathway

Abstract

BackgroundLung adenocarcinoma is the leading cause of cancer-related deaths among both men and women in the world. Despite recent advances in diagnosis and treatment, the mortality rates with an overall 5-year survival of only 15%. This high mortality is probably attributable to early metastasis. Although several well-known markers correlated with poor/metastasis prognosis in lung adenocarcinoma patients by immunohistochemistry was reported, the molecular mechanisms of lung adenocarcinoma development are still not clear. To explore novel molecular markers and their signaling pathways will be crucial for aiding in treatment of lung adenocarcinoma patients.Methodology/Principal FindingsTo identify novel lung adenocarcinoma-associated /metastasis genes and to clarify the underlying molecular mechanisms of these targets in lung cancer progression, we created a bioinformatics scheme consisting of integrating three gene expression profile datasets, including pairwise lung adenocarcinoma, secondary metastatic tumors vs. benign tumors, and a series of invasive cell lines. Among the novel targets identified, FLJ10540 was overexpressed in lung cancer tissues and is associated with cell migration and invasion. Furthermore, we employed two co-expression strategies to identify in which pathway FLJ10540 was involved. Lung adenocarcinoma array profiles and tissue microarray IHC staining data showed that FLJ10540 and VEGF-A, as well as FLJ10540 and phospho-AKT exhibit positive correlations, respectively. Stimulation of lung cancer cells with VEGF-A results in an increase in FLJ10540 protein expression and enhances complex formation with PI3K. Treatment with VEGFR2 and PI3K inhibitors affects cell migration and invasion by activating the PI3K/AKT pathway. Moreover, knockdown of FLJ10540 destabilizes formation of the P110-α/P85-α-(PI3K) complex, further supporting the participation of FLJ10540 in the VEGF-A/PI3K/AKT pathway.Conclusions/SignificanceThis finding set the stage for further testing of FLJ10540 as a new therapeutic target for treating lung cancer and may contribute to the development of new therapeutic strategies that are able to block the PI3K/AKT pathway in lung cancer cells.

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer

“…Public accessible microarray data (downloaded from Gene Expression Omnibus) were used to acquire different microarray data sets, which were normalized by Quantile Normalization using R to set up a potential metastatic biomarker identification platform. We compared 225 secondary metastatic tumors (including 20 tumor metastases to the lymph node and 200 metastatic tumors) and 30 benign tumors to obtain sets of potential promoters of metastasis, as described previously (Chen et al, 2009a). TOPK exhibits differential expression patterns, as shown by boxplot (Figure 1b, left).…”

“…In general, the transfection efficiency was B50-70%, except for IMR90 (B30%). At 24 or 48 h after transfection, cells were harvested and subjected to a migration, invasion or proliferation assay and the protein level of TOPK was determined by western blotting as described previously (Chen et al, 2009a).…”

Effects of matrine against the growth of human lung cancer and hepatoma cells as well as lung cancer cell migration

“…Statistically significant synergistic effect on the Bcl-2/Bax ratio was observed in A549 cells treated with MA50 ? TSA5 compared with the individual MA50 or TSA5 treatment alone (P \ 0.001, two-way ANOVA) lung cancer via the PI3K/AKT pathway (Chen et al 2009). Hence, we investigated the effects of matrine on the VEGF-A secretion in A549 cells.…”

Use of an Artificial Neural Network to Predict Risk Factors of Nosocomial Infection in Lung Cancer Patients

“…Despite surgical resection, chemotherapy and radiation therapy technology are continuously improving, patientswith lung cancer remains extremely vulnerable to relapse and fatal (Gridelli et al, 2003). The cure rate of lung cancer is very low and the average 5-year survival of patients with lung cancer is below 15 % ( Ogawa et al, 2008;Rachet et al, 2008;Chen et al, 2009;Stewart et al, 2010). The nosocomial infection rate of patients with lung cancer showed high trend (Kamboj et al, 2009).…”