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Published on: May 19, 2016
PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating
Bin Wang1, Lin-Yue Pan2, Ning Kang1
1Department of Thoracic Surgery, The Affiliated Huadong Hospital of Fudan University, Shanghai, China.
Abstract:
Protein phosphatase 4 regulatory subunit 1 (PP4R1) has been shown to play a role in the regulation of centrosome maturation, apoptosis, DNA repair, and tumor necrosis factor signaling. However, the function of PP4R1 in non-small-cell lung cancer remains unclear. In this study, we identify PP4R1 as an oncogene through Oncomine database mining and immunohistochemical staining, and we showed that PP4R1 is upregulated in lung cancer tissues as compared with that in normal lung tissues and correlated with a poor prognosis in lung cancer patients. Furthermore, in vitro study by wound-healing and Transwell assay showed that PP4R1 could promote migration and invasion of lung cancer cells. Mechanistic investigations revealed that PP4R1 could cooperate with high mobility group AT-hook 2 and thereby promotes epithelial-mesenchymal transition via MAPK/extracellular receptor kinase activation. Taken together, our study provides a rich resource for understanding PP4R1 in lung cancer and indicates that PP4R1 may serve as a potential biomarker in lung cancer therapies.
Insights
Protein phosphatase 4 regulatory subunit 1 (PP4R1) is upregulated in non-small-cell lung cancer, promoting cell migration and invasion. This study identifies PP4R1 as a potential oncogene and therapeutic target for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Protein phosphatase 4 regulatory subunit 1 (PP4R1) is involved in cell cycle regulation, DNA repair, and apoptosis.
- The specific role of PP4R1 in non-small-cell lung cancer (NSCLC) pathogenesis is not well understood.
Purpose of the Study:
- To investigate the role and clinical significance of PP4R1 in non-small-cell lung cancer.
- To elucidate the underlying molecular mechanisms by which PP4R1 influences NSCLC progression.
Main Methods:
- Oncomine database mining and immunohistochemical staining to assess PP4R1 expression in NSCLC tissues.
- In vitro assays (wound-healing, Transwell) to evaluate the effect of PP4R1 on NSCLC cell migration and invasion.
- Mechanistic studies to explore the interaction of PP4R1 with other proteins and signaling pathways (MAPK/ERK).
Main Results:
- PP4R1 is significantly upregulated in NSCLC tissues compared to normal lung tissues.
- High PP4R1 expression correlates with poor prognosis in NSCLC patients.
- PP4R1 overexpression promotes NSCLC cell migration and invasion.
- PP4R1 cooperates with high mobility group AT-hook 2 to drive epithelial-mesenchymal transition via MAPK/ERK activation.
Conclusions:
- PP4R1 functions as an oncogene in non-small-cell lung cancer.
- PP4R1 promotes NSCLC progression by enhancing cell migration, invasion, and epithelial-mesenchymal transition.
- PP4R1 represents a potential diagnostic biomarker and therapeutic target for NSCLC.
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