Abstract
Protein kinase D2 (PKD2) has been reported to be related with progression and invasion in various cancers. However, its prognostic value and the underlying mechanism in lung cancer remains unclear. Herein we evaluated the expression of PKD2 in lung adenocarcinoma and investigated its relationship with EMT. GSEA, TCGA and K-M plotter database were applied and revealed that high PKD2 expression predicted poor outcome and related with lymph nodes metastasis in lung cancer. IHC and qRT-PCR were performed and found PKD2 was elevated in lung adenocarcinoma and negatively related with OS (p = 0.015), PFS (p = 0.006) and the level of E-cadherin (p = 0.021). Experiment in lung adenocarcinoma cell lines demonstrated up-regulation of PKD2 led to high expression of mesenchymal markers (N-cadherin, vim, mmp9 et al.) and EMT transcription factors(zeb1, twist, snail), and the results were reversed when PKD2 was knocked down. Further investigation showed that abrogation of PKD2 inhibited A549 cell migration, invasion, proliferation and induced cell arrest in G2/M phase. We concluded that high expression of PKD2 was associated with poor prognosis and cancer progression in lung adenocarcinoma patients by promoting EMT.
Highlights
Lung cancer is the most common malignancy with high mortality worldwide[1,2]
To explore oncogenic signaling related to Protein kinase D2 (PKD2), we performed GSEA and found that Non-small cell lung cancer (NSCLC) related genes were mainly enriched in tumors with high level of PKD2 (Fig. 1A)
The data extracted from TCGA showed that high expression of PKD2 was significantly related with lymph nodes metastasis with p < 0.001 (Fig. 1C)
Summary
Lung cancer is the most common malignancy with high mortality worldwide[1,2]. Non-small cell lung cancer (NSCLC), which is less destructive but more prevalent than small cell lung cancer, accounts for more than 80% of lung cancer. PKD2 was found to be capable to orchestrate cancer cell proliferation, survival, angiogenesis, motility and immune response by regulating multiple signaling pathways (e.g., MEK/ERK, NF-κB), as well as integrating extracellular signals (e.g., signals from hypoxia, growth factors)[25,26]. These years, studies about PKDs and EMT have been reported, and it is proved that PKDs have different effects on this transition process[27]. We performed this study in order to evaluate the underlying roles and mechanisms of PKD2 in tumorigenesis of lung adenocarcinoma
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call