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Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses

BACKGROUND: Lung cancer is still the main cause of death in patients with cancer, due to poor understanding of intracellular regulations. Of those, osteopontin (OPN) may induce the epithelial‐to‐mesenchymal transition (EMT) to promote tumor cell metastasis. The present study aims to evaluate the reg...

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Autores principales: Shi, Lin, Hou, Jiayun, Wang, Lin, Fu, Huirong, Zhang, Yiwen, Song, Yuanlin, Wang, Xiangdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265167/
https://www.ncbi.nlm.nih.gov/pubmed/34323425
http://dx.doi.org/10.1002/ctm2.486
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author Shi, Lin
Hou, Jiayun
Wang, Lin
Fu, Huirong
Zhang, Yiwen
Song, Yuanlin
Wang, Xiangdong
author_facet Shi, Lin
Hou, Jiayun
Wang, Lin
Fu, Huirong
Zhang, Yiwen
Song, Yuanlin
Wang, Xiangdong
author_sort Shi, Lin
collection PubMed
description BACKGROUND: Lung cancer is still the main cause of death in patients with cancer, due to poor understanding of intracellular regulations. Of those, osteopontin (OPN) may induce the epithelial‐to‐mesenchymal transition (EMT) to promote tumor cell metastasis. The present study aims to evaluate the regulatory mechanism of internal and external OPN in the development of lung cancer. METHODS: We evaluated genetic variations and different bioinformatics of genes in chromosome 4 among subtypes of lung cancer using global databases. We validated the expression of OPN and EMT‐related proteins (e.g., E‐cadherin, vimentin) in 208 non‐small‐cell lung cancer (NSCLC) tumors and the adjacent nontumorous tissues, further to explore the function of OPN in the progression of lung cancer, with a focus on a potential communication between OPN and EMT in the lung cancer. RESULTS: We found that OPN might act as a target molecule in lung cancer, which is associated with lymph node metastasis, postresection recurrence/metastasis, and prognosis of patients with lung cancer. Biological behaviors and pathological responses of OPN varied among diseases, challenges, and severities. Overexpression of OPN was correlated with the existence of EMT in lung cancer tissues. Internal and external OPN plays the decisive roles in lung cancer cell movement, proliferation, and EMT formation, through the upregulation of OPN‐PI3K and OPN‐MEK pathways. PI3K and MEK inhibitors downregulated the process of EMT and biological behaviors of lung cancer cells, probably through altering vimentin‐associated cytoskeletons. CONCLUSION: OPN can be a metastasis‐associated or specific biomarker for lung cancer and a potential target for antimetastatic treatment.
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spelling pubmed-82651672021-07-13 Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses Shi, Lin Hou, Jiayun Wang, Lin Fu, Huirong Zhang, Yiwen Song, Yuanlin Wang, Xiangdong Clin Transl Med Research Articles BACKGROUND: Lung cancer is still the main cause of death in patients with cancer, due to poor understanding of intracellular regulations. Of those, osteopontin (OPN) may induce the epithelial‐to‐mesenchymal transition (EMT) to promote tumor cell metastasis. The present study aims to evaluate the regulatory mechanism of internal and external OPN in the development of lung cancer. METHODS: We evaluated genetic variations and different bioinformatics of genes in chromosome 4 among subtypes of lung cancer using global databases. We validated the expression of OPN and EMT‐related proteins (e.g., E‐cadherin, vimentin) in 208 non‐small‐cell lung cancer (NSCLC) tumors and the adjacent nontumorous tissues, further to explore the function of OPN in the progression of lung cancer, with a focus on a potential communication between OPN and EMT in the lung cancer. RESULTS: We found that OPN might act as a target molecule in lung cancer, which is associated with lymph node metastasis, postresection recurrence/metastasis, and prognosis of patients with lung cancer. Biological behaviors and pathological responses of OPN varied among diseases, challenges, and severities. Overexpression of OPN was correlated with the existence of EMT in lung cancer tissues. Internal and external OPN plays the decisive roles in lung cancer cell movement, proliferation, and EMT formation, through the upregulation of OPN‐PI3K and OPN‐MEK pathways. PI3K and MEK inhibitors downregulated the process of EMT and biological behaviors of lung cancer cells, probably through altering vimentin‐associated cytoskeletons. CONCLUSION: OPN can be a metastasis‐associated or specific biomarker for lung cancer and a potential target for antimetastatic treatment. John Wiley and Sons Inc. 2021-07-08 /pmc/articles/PMC8265167/ /pubmed/34323425 http://dx.doi.org/10.1002/ctm2.486 Text en © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Shi, Lin
Hou, Jiayun
Wang, Lin
Fu, Huirong
Zhang, Yiwen
Song, Yuanlin
Wang, Xiangdong
Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses
title Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses
title_full Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses
title_fullStr Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses
title_full_unstemmed Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses
title_short Regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses
title_sort regulatory roles of osteopontin in human lung cancer cell epithelial‐to‐mesenchymal transitions and responses
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265167/
https://www.ncbi.nlm.nih.gov/pubmed/34323425
http://dx.doi.org/10.1002/ctm2.486
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