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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...

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Autores principales: Chen, Bo, Liang, Yan, Chen, Liben, Wei, Yunyan, Li, Yue, Zhao, Weihong, Wu, Jianqing
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
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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.
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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
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