PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition.

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.

• Authors: Bin Wang, Lin-Yue Pan, Ning Kang, Xiao-Yong Shen
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 59 Issue 5 Pg. 467-477 (05 2020) ISSN: 1098-2744 [Electronic] United States
• PMID: 32077156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• Biomarkers, Tumor
• HMGA2 Protein
• HMGA2 protein, human
• MAPK1 protein, human
• MAPK3 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Phosphoprotein Phosphatases
• protein phosphatase 4

Topics

• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, secondary)
• Cell Movement
• Cell Proliferation
• Epithelial-Mesenchymal Transition
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• HMGA2 Protein (genetics, metabolism)
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Male
• Middle Aged
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Neoplasm Invasiveness
• Phosphoprotein Phosphatases (genetics, metabolism)
• Prognosis
• Survival Rate
• Tumor Cells, Cultured