Abstract
BackgroundGrowing evidence indicates that high phosphoserine phosphatase (PSPH) expression is associated with tumor prognosis in many types of cancers. However, the role of PSPH in non‐small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the clinical significance of PSPH in NSCLC.MethodsOne hundred forty‐three patients with histologically confirmed NSCLC who underwent surgery were included. Quantitative real‐time PCR and Western blot were used to assess PSPH expression in paired tumor and corresponding adjacent non‐tumorous tissues. The role of PSPH in invasion and cell growth was investigated in vitro.ResultsCompared to adjacent normal lung tissues, PSPH messenger RNA and protein levels were significantly higher in NSCLC tissues, and the PSPH expression level was positively related to clinical stage, metastasis, and recurrence. High PSPH expression was predictive of poor overall survival. A549 cells transfected with small interfering‐PSPH showed inhibited cell migration, invasion, and proliferation. We further demonstrated that PSPH might promote the invasive capabilities of NSCLC cells through the AKT/AMPK signaling pathway.ConclusionOur results indicate that PSPH may act as a putative oncogene in NSCLC, and may be a vital molecular marker for the metastasis and proliferation of NSCLC cells by regulating the AKT/AMPK signaling pathway.
Highlights
Lung cancer is the most lethal solid tumor and the leading cause of cancer-related death worldwide,[1,2] with both median follow-up and overall survival (OS) rates in all patients of > 14 months after initial diagnosis.[3]
We investigated the prognostic effect of PSPH in non-small cell lung cancer (NSCLC) and determined the role of PSPH in NSCLC cell proliferation and metastasis
To explore the possible downstream signaling pathways by which PSPH modulates the progression of NSCLC cells, we investigated the effects of PSPH on cell survival, proliferation, invasion, and metastasis-related signaling molecules in A549 cells after si-PSPH transfection, including mTOR, FAK, Stat[3], AMPK, AKT, and JNK
Summary
Lung cancer is the most lethal solid tumor and the leading cause of cancer-related death worldwide,[1,2] with both median follow-up and overall survival (OS) rates in all patients of > 14 months after initial diagnosis.[3]. Growing evidence indicates that high phosphoserine phosphatase (PSPH) expression is associated with tumor prognosis in many types of cancers. The role of PSPH in non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the clinical significance of PSPH in NSCLC. Results: Compared to adjacent normal lung tissues, PSPH messenger RNA and protein levels were significantly higher in NSCLC tissues, and the PSPH expression level was positively related to clinical stage, metastasis, and recurrence. We further demonstrated that PSPH might promote the invasive capabilities of NSCLC cells through the AKT/AMPK signaling pathway. Conclusion: Our results indicate that PSPH may act as a putative oncogene in NSCLC, and may be a vital molecular marker for the metastasis and proliferation of NSCLC cells by regulating the AKT/AMPK signaling pathway
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