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© 2022 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway
Author
Li, Hao 1 ; Qiu, Lei 1 ; Liu, Qing 1 ; Ma, Zelong 1 ; Xie, Xiaoli 1 ; Luo, Ying 2 ; Wu, Xiaoming 1 

 Laboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and Technology, Chenggong Campus, 727 South Jingming Road, Kunming 650500, China 
 Guizhou Provincial Key Laboratory of Pathogenesis & Drug Development on Common Chronic Diseases, School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China 
First page
1579
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
20734425
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2716540249
Copyright
© 2022 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.