FAK Executes Anti-Senescence via Regulating EZH2 Signaling in Non-Small Cell Lung Cancer Cells

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase overexpressed in various cancer types that plays a critical role in tumor progression. Accumulating evidence suggests that targeting FAK, either alone or in combination with other agents, may serve as an effective therapeutic strategy for...

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Published inBiomedicines Vol. 10; no. 8; p. 1937
Main Authors Chuang, Hsiang-Hao, Huang, Ming-Shyan, Zhen, Yen-Yi, Chuang, Cheng-Hao, Lee, Ying-Ray, Hsiao, Michael, Yang, Chih-Jen
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.08.2022
MDPI
Subjects
Angiogenesis
Antibodies
Cancer therapies
Cell cycle
Cell growth
Cyclin-dependent kinases
DNA damage
Epigenetics
Experiments
EZH2
FAK
Focal adhesion kinase
Immunohistochemistry
Kinases
lamin A/C
Lung cancer
Lung cancer, Non-small cell
Medical prognosis
Metastases
Non-small cell lung carcinoma
Physiological aspects
Protein-tyrosine kinase receptors
Proteins
Senescence
Small cell lung carcinoma
Taiwan
Hungary
United States > US
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Summary:Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase overexpressed in various cancer types that plays a critical role in tumor progression. Accumulating evidence suggests that targeting FAK, either alone or in combination with other agents, may serve as an effective therapeutic strategy for numerous cancers. In addition to retarding proliferation, metastasis, and angiogenesis, FAK inhibition triggers cellular senescence in lung cancer cells. However, the detailed mechanism remains enigmatic. In the present study, we found that FAK inhibition not only elicits DNA-damage signaling but also downregulates enhancer of zeste homolog 2 (EZH2) expression. The manipulation of FAK expression influences EZH2 expression and corresponding signaling in vitro. Immunohistochemistry shows that active FAK signaling corresponds with the activation of the EZH2-mediated signaling cascade in lung-cancer-cells-derived tumor tissues. We also found that ectopic EZH2 expression attenuates FAK-inhibition-induced cellular senescence in lung cancer cells. Our results identify EZH2 as a critical downstream effector of the FAK-mediated anti-senescence pathway. Targeting FAK-EZH2 axis-induced cellular senescence may represent a promising therapeutic strategy for restraining tumor growth.
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These authors contributed equally to this work.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines10081937