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Effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells
PURPOSE: To explore the effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on the proliferation, invasion, and migration of human osteosarcoma cells. METHODS: The expression of PAK4/LIMK1/Cofilin‐1 was detected by immunohistochemistry in osteosarcoma tissues. The osteosarcoma cell line MG63 was trans...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521293/ https://www.ncbi.nlm.nih.gov/pubmed/32463132 http://dx.doi.org/10.1002/jcla.23362 |
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author | Li, Zhi‐Feng Yao, Yin‐Di Zhao, Yin‐Yin Liu, Yan Liu, Zhen‐Hua Hu, Pei Zhu, Zhuo‐Ran |
author_facet | Li, Zhi‐Feng Yao, Yin‐Di Zhao, Yin‐Yin Liu, Yan Liu, Zhen‐Hua Hu, Pei Zhu, Zhuo‐Ran |
author_sort | Li, Zhi‐Feng |
collection | PubMed |
description | PURPOSE: To explore the effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on the proliferation, invasion, and migration of human osteosarcoma cells. METHODS: The expression of PAK4/LIMK1/Cofilin‐1 was detected by immunohistochemistry in osteosarcoma tissues. The osteosarcoma cell line MG63 was transfected and divided into Mock, Control siRNA, si‐PAK4, LIMK1, and si‐PAK4+LIMK1 groups. Then, the cellular biological features of MG63 cells were detected by CCK‐8, wound‐healing, Transwell, and flow cytometry methods. The relationship of PAK4 and LIMK1 was performed by co‐immunoprecipitation test, and the protein expression of PAK4/LIMK1/Cofilin‐1 was determined by Western blotting. Finally, the effect of PAK4 on the growth of osteosarcoma was verified by subcutaneous transplantation model of osteosarcoma in nude mice. RESULTS: The expression of PAK4/LIMK1/Cofilin‐1 in both osteosarcoma tissues and cells was up‐regulated. Positive PAK4, LIMK1, and Cofilin‐1 expressions in osteosarcoma were associated with the clinical stage, distant metastasis, and tumor grade. The MG63 cell viability, migration, and invasion, as well as the expression of PAK4, p‐LIMK/LIMK, and p‐Cofilin‐1/Cofilin‐1, were restrained by the knock down of PAK4 while it promoted apoptosis. PAK4 silencing also suppressed the growth of subcutaneous transplanted tumor in nude mice. Co‐immunocoprecipitation showed that LIMK and PAK4 protein can form complex in osteosarcoma cells. Besides, LIMK1 overexpression reversed the inhibition effect of PAK4 siRNA on the growth of osteosarcoma cells. CONCLUSION: The expression of PAK4/LIMK1/Cofilin‐1 pathway in osteosarcoma tissues was up‐regulated. Thus, PAK4 inhibition may restrict the osteosarcoma cell proliferation, invasion, and migration but promote its apoptosis via decreasing the activity of LIMK1/Cofilin‐1 pathway. |
format | Online Article Text |
id | pubmed-7521293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75212932020-10-02 Effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells Li, Zhi‐Feng Yao, Yin‐Di Zhao, Yin‐Yin Liu, Yan Liu, Zhen‐Hua Hu, Pei Zhu, Zhuo‐Ran J Clin Lab Anal Research Articles PURPOSE: To explore the effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on the proliferation, invasion, and migration of human osteosarcoma cells. METHODS: The expression of PAK4/LIMK1/Cofilin‐1 was detected by immunohistochemistry in osteosarcoma tissues. The osteosarcoma cell line MG63 was transfected and divided into Mock, Control siRNA, si‐PAK4, LIMK1, and si‐PAK4+LIMK1 groups. Then, the cellular biological features of MG63 cells were detected by CCK‐8, wound‐healing, Transwell, and flow cytometry methods. The relationship of PAK4 and LIMK1 was performed by co‐immunoprecipitation test, and the protein expression of PAK4/LIMK1/Cofilin‐1 was determined by Western blotting. Finally, the effect of PAK4 on the growth of osteosarcoma was verified by subcutaneous transplantation model of osteosarcoma in nude mice. RESULTS: The expression of PAK4/LIMK1/Cofilin‐1 in both osteosarcoma tissues and cells was up‐regulated. Positive PAK4, LIMK1, and Cofilin‐1 expressions in osteosarcoma were associated with the clinical stage, distant metastasis, and tumor grade. The MG63 cell viability, migration, and invasion, as well as the expression of PAK4, p‐LIMK/LIMK, and p‐Cofilin‐1/Cofilin‐1, were restrained by the knock down of PAK4 while it promoted apoptosis. PAK4 silencing also suppressed the growth of subcutaneous transplanted tumor in nude mice. Co‐immunocoprecipitation showed that LIMK and PAK4 protein can form complex in osteosarcoma cells. Besides, LIMK1 overexpression reversed the inhibition effect of PAK4 siRNA on the growth of osteosarcoma cells. CONCLUSION: The expression of PAK4/LIMK1/Cofilin‐1 pathway in osteosarcoma tissues was up‐regulated. Thus, PAK4 inhibition may restrict the osteosarcoma cell proliferation, invasion, and migration but promote its apoptosis via decreasing the activity of LIMK1/Cofilin‐1 pathway. John Wiley and Sons Inc. 2020-05-28 /pmc/articles/PMC7521293/ /pubmed/32463132 http://dx.doi.org/10.1002/jcla.23362 Text en © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Li, Zhi‐Feng Yao, Yin‐Di Zhao, Yin‐Yin Liu, Yan Liu, Zhen‐Hua Hu, Pei Zhu, Zhuo‐Ran Effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells |
title | Effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells |
title_full | Effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells |
title_fullStr | Effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells |
title_full_unstemmed | Effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells |
title_short | Effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells |
title_sort | effects of pak4/limk1/cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521293/ https://www.ncbi.nlm.nih.gov/pubmed/32463132 http://dx.doi.org/10.1002/jcla.23362 |
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