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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...

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Autores principales: Li, Hao, Qiu, Lei, Liu, Qing, Ma, Zelong, Xie, Xiaoli, Luo, Ying, Wu, Xiaoming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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