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PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin
PURPOSE: The significance of periodic tryptophan protein 1 (PWP1) expression in human cancer and its molecular mechanism of action have not been reported so far. MATERIALS AND METHODS: Immunohistochemistry was performed to analyze the expression of PWP1 in non-small cell lung cancer (NSCLC) tissues...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553635/ https://www.ncbi.nlm.nih.gov/pubmed/33116587 http://dx.doi.org/10.2147/OTT.S263815 |
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author | Wei, Lai Li, Pengcheng Luo, Yuan Zhang, Meiyu Yan, Ting Yang, Yue Han, Yuchen Liu, Shuli Wang, Enhua |
author_facet | Wei, Lai Li, Pengcheng Luo, Yuan Zhang, Meiyu Yan, Ting Yang, Yue Han, Yuchen Liu, Shuli Wang, Enhua |
author_sort | Wei, Lai |
collection | PubMed |
description | PURPOSE: The significance of periodic tryptophan protein 1 (PWP1) expression in human cancer and its molecular mechanism of action have not been reported so far. MATERIALS AND METHODS: Immunohistochemistry was performed to analyze the expression of PWP1 in non-small cell lung cancer (NSCLC) tissues and statistical analysis was applied to analyze the relationship between PWP1 expression and the clinicopathological factors. The effects of PWP1 on NSCLC proliferation and invasion were determined by colony formation, transwell and MTT assays. Western blot analysis (WB), dual-luciferase reporter gene assays and immunofluorescence staining were performed to demonstrate whether PWP1 stimulates Wnt pathway and inhibits Hippo pathway. Co-immunoprecipitation (Co-ip) assays were used to confirm the potential role of PWP1 in Wnt and Hippo signaling pathways. RESULTS: PWP1 expression in NSCLC was higher than that in normal bronchial epithelium and normal submucosal glands. In addition, PWP1 expression had a positive correlation with poor differentiation, high pathological tumor-node-metastasis (TNM) stage, and lymph node metastasis. Kaplan–Meier database demonstrated that the overall survival time of patients with high PWP1 expression was significantly shorter than that of patients with low PWP1 expression. Mechanistically, we found that PWP1 could interact with DVL2 to upregulate β-catenin (thereby activating the Wnt pathway), whereas PWP1 could interact with Merlin (NF2) to downregulate p-MST1 (thereby inhibiting the Hippo signaling pathway). The effects of PWP1 on promoting the Wnt pathway or inhibiting the Hippo pathway were offset in DVL2- or Merlin-knockdown cells transiently overexpressing PWP1. CONCLUSION: PWP1 expression in NSCLC was correlated with poor prognosis. PWP1 enhanced the activity of the Wnt pathway by interacting with DVL2, whereas PWP1 inhibited the activity of the Hippo pathway by interacting with Merlin. Together, these two effects promoted the detrimental biological behaviors of NSCLC cells. |
format | Online Article Text |
id | pubmed-7553635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-75536352020-10-27 PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin Wei, Lai Li, Pengcheng Luo, Yuan Zhang, Meiyu Yan, Ting Yang, Yue Han, Yuchen Liu, Shuli Wang, Enhua Onco Targets Ther Original Research PURPOSE: The significance of periodic tryptophan protein 1 (PWP1) expression in human cancer and its molecular mechanism of action have not been reported so far. MATERIALS AND METHODS: Immunohistochemistry was performed to analyze the expression of PWP1 in non-small cell lung cancer (NSCLC) tissues and statistical analysis was applied to analyze the relationship between PWP1 expression and the clinicopathological factors. The effects of PWP1 on NSCLC proliferation and invasion were determined by colony formation, transwell and MTT assays. Western blot analysis (WB), dual-luciferase reporter gene assays and immunofluorescence staining were performed to demonstrate whether PWP1 stimulates Wnt pathway and inhibits Hippo pathway. Co-immunoprecipitation (Co-ip) assays were used to confirm the potential role of PWP1 in Wnt and Hippo signaling pathways. RESULTS: PWP1 expression in NSCLC was higher than that in normal bronchial epithelium and normal submucosal glands. In addition, PWP1 expression had a positive correlation with poor differentiation, high pathological tumor-node-metastasis (TNM) stage, and lymph node metastasis. Kaplan–Meier database demonstrated that the overall survival time of patients with high PWP1 expression was significantly shorter than that of patients with low PWP1 expression. Mechanistically, we found that PWP1 could interact with DVL2 to upregulate β-catenin (thereby activating the Wnt pathway), whereas PWP1 could interact with Merlin (NF2) to downregulate p-MST1 (thereby inhibiting the Hippo signaling pathway). The effects of PWP1 on promoting the Wnt pathway or inhibiting the Hippo pathway were offset in DVL2- or Merlin-knockdown cells transiently overexpressing PWP1. CONCLUSION: PWP1 expression in NSCLC was correlated with poor prognosis. PWP1 enhanced the activity of the Wnt pathway by interacting with DVL2, whereas PWP1 inhibited the activity of the Hippo pathway by interacting with Merlin. Together, these two effects promoted the detrimental biological behaviors of NSCLC cells. Dove 2020-10-08 /pmc/articles/PMC7553635/ /pubmed/33116587 http://dx.doi.org/10.2147/OTT.S263815 Text en © 2020 Wei et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wei, Lai Li, Pengcheng Luo, Yuan Zhang, Meiyu Yan, Ting Yang, Yue Han, Yuchen Liu, Shuli Wang, Enhua PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin |
title | PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin |
title_full | PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin |
title_fullStr | PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin |
title_full_unstemmed | PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin |
title_short | PWP1 Promotes the Malignant Phenotypes of Lung Cancer Cells by Interacting with DVL2 and Merlin |
title_sort | pwp1 promotes the malignant phenotypes of lung cancer cells by interacting with dvl2 and merlin |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553635/ https://www.ncbi.nlm.nih.gov/pubmed/33116587 http://dx.doi.org/10.2147/OTT.S263815 |
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