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Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway
Aging has been recently reported to promote lung cancer initiation and progression. Senescent fibroblasts gain a cancer-associated fibroblast (CAF) phenotype, and exert a powerful influence on cancer behavior, such as tumor cell growth and metastasis. However, mechanisms linking fibroblast senescenc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498467/ https://www.ncbi.nlm.nih.gov/pubmed/36140747 http://dx.doi.org/10.3390/genes13091579 |
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author | Li, Hao Qiu, Lei Liu, Qing Ma, Zelong Xie, Xiaoli Luo, Ying Wu, Xiaoming |
author_facet | Li, Hao Qiu, Lei Liu, Qing Ma, Zelong Xie, Xiaoli Luo, Ying Wu, Xiaoming |
author_sort | Li, Hao |
collection | PubMed |
description | Aging has been recently reported to promote lung cancer initiation and progression. Senescent fibroblasts gain a cancer-associated fibroblast (CAF) phenotype, and exert a powerful influence on cancer behavior, such as tumor cell growth and metastasis. However, mechanisms linking fibroblast senescence with CAF activation remain poorly understood. Our study shows that senescent fibroblasts displayed CAF properties, including the highly expressed CAF markers, α-SMA and Vimentin, and CAF-specific factors, CXCL12, FGF10, IL6 and COL1A1, which significantly increased collagen contractile activity and promoted the migration and invasion of lung cancer cells, H1299 and A549. We were further able to show that CAF characteristics in senescent fibroblasts could be regulated by the Stat3 pathway. Intracellular ROS accumulation activates the Stat3 pathway during senescence. Thus, our findings indicate that senescent fibroblasts mediate a CAF function with the Stat3 pathway. We further propose a novel Stat3 dependent targetable mechanism, which is instrumental in mediating the migration and invasion of lung cancer cells. |
format | Online Article Text |
id | pubmed-9498467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94984672022-09-23 Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway Li, Hao Qiu, Lei Liu, Qing Ma, Zelong Xie, Xiaoli Luo, Ying Wu, Xiaoming Genes (Basel) Article Aging has been recently reported to promote lung cancer initiation and progression. Senescent fibroblasts gain a cancer-associated fibroblast (CAF) phenotype, and exert a powerful influence on cancer behavior, such as tumor cell growth and metastasis. However, mechanisms linking fibroblast senescence with CAF activation remain poorly understood. Our study shows that senescent fibroblasts displayed CAF properties, including the highly expressed CAF markers, α-SMA and Vimentin, and CAF-specific factors, CXCL12, FGF10, IL6 and COL1A1, which significantly increased collagen contractile activity and promoted the migration and invasion of lung cancer cells, H1299 and A549. We were further able to show that CAF characteristics in senescent fibroblasts could be regulated by the Stat3 pathway. Intracellular ROS accumulation activates the Stat3 pathway during senescence. Thus, our findings indicate that senescent fibroblasts mediate a CAF function with the Stat3 pathway. We further propose a novel Stat3 dependent targetable mechanism, which is instrumental in mediating the migration and invasion of lung cancer cells. MDPI 2022-09-02 /pmc/articles/PMC9498467/ /pubmed/36140747 http://dx.doi.org/10.3390/genes13091579 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Hao Qiu, Lei Liu, Qing Ma, Zelong Xie, Xiaoli Luo, Ying Wu, Xiaoming Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway |
title | Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway |
title_full | Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway |
title_fullStr | Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway |
title_full_unstemmed | Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway |
title_short | Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway |
title_sort | senescent fibroblasts generate a caf phenotype through the stat3 pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498467/ https://www.ncbi.nlm.nih.gov/pubmed/36140747 http://dx.doi.org/10.3390/genes13091579 |
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