Cargando…
Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells
Lung cancer (LC) is the most common cause of death from cancer worldwide, and it is also a closely aging-related disease. Klotho, a new anti-aging gene, has been proven to play a critical role in regulating aging and the development of age-related diseases including LC. However, whether Klotho is a...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907673/ https://www.ncbi.nlm.nih.gov/pubmed/29675106 http://dx.doi.org/10.7150/jca.23967 |
_version_ | 1783315581660823552 |
---|---|
author | Chen, Bo Liang, Yan Chen, Liben Wei, Yunyan Li, Yue Zhao, Weihong Wu, Jianqing |
author_facet | Chen, Bo Liang, Yan Chen, Liben Wei, Yunyan Li, Yue Zhao, Weihong Wu, Jianqing |
author_sort | Chen, Bo |
collection | PubMed |
description | Lung cancer (LC) is the most common cause of death from cancer worldwide, and it is also a closely aging-related disease. Klotho, a new anti-aging gene, has been proven to play a critical role in regulating aging and the development of age-related diseases including LC. However, whether Klotho is a key link between aging and LC is still unknown. Here we report that Klotho can indirectly inhibit LC growth and development through regulating senescence-associated secretory phenotype (SASP). We found that senescent lung fibroblasts (SLF) can promote production of IL-6 and IL-8, which can be effectively inhibited by overexpressing Klotho. Using conditioned medium (CM) derived from SLF to culture LC cells, the LC cells show obvious increase of viability and migration rates, significant increase expression of p-STAT3 and α-SMA, and decrease expression of P53 and E-cadherin. However, using CM derived from SLF overexpressed Klotho to culture LC cells, all above results are nearly completely reversed. Thus, these results suggest that Klotho can regulate SLF extracellular release of IL-6 and IL-8, which can influence STAT3 activation, P53 expression and epithelial-mesenchymal transition (EMT) of LC cells, finally inhibiting LC cells growth and migration indirectly. |
format | Online Article Text |
id | pubmed-5907673 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-59076732018-04-19 Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells Chen, Bo Liang, Yan Chen, Liben Wei, Yunyan Li, Yue Zhao, Weihong Wu, Jianqing J Cancer Research Paper Lung cancer (LC) is the most common cause of death from cancer worldwide, and it is also a closely aging-related disease. Klotho, a new anti-aging gene, has been proven to play a critical role in regulating aging and the development of age-related diseases including LC. However, whether Klotho is a key link between aging and LC is still unknown. Here we report that Klotho can indirectly inhibit LC growth and development through regulating senescence-associated secretory phenotype (SASP). We found that senescent lung fibroblasts (SLF) can promote production of IL-6 and IL-8, which can be effectively inhibited by overexpressing Klotho. Using conditioned medium (CM) derived from SLF to culture LC cells, the LC cells show obvious increase of viability and migration rates, significant increase expression of p-STAT3 and α-SMA, and decrease expression of P53 and E-cadherin. However, using CM derived from SLF overexpressed Klotho to culture LC cells, all above results are nearly completely reversed. Thus, these results suggest that Klotho can regulate SLF extracellular release of IL-6 and IL-8, which can influence STAT3 activation, P53 expression and epithelial-mesenchymal transition (EMT) of LC cells, finally inhibiting LC cells growth and migration indirectly. Ivyspring International Publisher 2018-03-14 /pmc/articles/PMC5907673/ /pubmed/29675106 http://dx.doi.org/10.7150/jca.23967 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Chen, Bo Liang, Yan Chen, Liben Wei, Yunyan Li, Yue Zhao, Weihong Wu, Jianqing Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells |
title | Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells |
title_full | Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells |
title_fullStr | Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells |
title_full_unstemmed | Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells |
title_short | Overexpression of Klotho Inhibits HELF Fibroblasts SASP-related Protumoral Effects on Non-small Cell Lung Cancer Cells |
title_sort | overexpression of klotho inhibits helf fibroblasts sasp-related protumoral effects on non-small cell lung cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907673/ https://www.ncbi.nlm.nih.gov/pubmed/29675106 http://dx.doi.org/10.7150/jca.23967 |
work_keys_str_mv | AT chenbo overexpressionofklothoinhibitshelffibroblastssasprelatedprotumoraleffectsonnonsmallcelllungcancercells AT liangyan overexpressionofklothoinhibitshelffibroblastssasprelatedprotumoraleffectsonnonsmallcelllungcancercells AT chenliben overexpressionofklothoinhibitshelffibroblastssasprelatedprotumoraleffectsonnonsmallcelllungcancercells AT weiyunyan overexpressionofklothoinhibitshelffibroblastssasprelatedprotumoraleffectsonnonsmallcelllungcancercells AT liyue overexpressionofklothoinhibitshelffibroblastssasprelatedprotumoraleffectsonnonsmallcelllungcancercells AT zhaoweihong overexpressionofklothoinhibitshelffibroblastssasprelatedprotumoraleffectsonnonsmallcelllungcancercells AT wujianqing overexpressionofklothoinhibitshelffibroblastssasprelatedprotumoraleffectsonnonsmallcelllungcancercells |