Autor: |
Fenghua Bian, Chinmayee Goda, Guolun Wang, Ying-Wei Lan, Zicheng Deng, Wen Gao, Anusha Acharya, Abid A Reza, Jose Gomez-Arroyo, Nawal Merjaneh, Xiaomeng Ren, Jermaine Goveia, Peter Carmeliet, Vladimir V Kalinichenko, Tanya V Kalin |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
EMBO Molecular Medicine, Vol 16, Iss 5, Pp 1063-1090 (2024) |
Druh dokumentu: |
article |
ISSN: |
1757-4684 |
DOI: |
10.1038/s44321-024-00064-8 |
Popis: |
Abstract Cancer cells re-program normal lung endothelial cells (EC) into tumor-associated endothelial cells (TEC) that form leaky vessels supporting carcinogenesis. Transcriptional regulators that control the reprogramming of EC into TEC are poorly understood. We identified Forkhead box F1 (FOXF1) as a critical regulator of EC-to-TEC transition. FOXF1 was highly expressed in normal lung vasculature but was decreased in TEC within non-small cell lung cancers (NSCLC). Low FOXF1 correlated with poor overall survival of NSCLC patients. In mice, endothelial-specific deletion of FOXF1 decreased pericyte coverage, increased vessel permeability and hypoxia, and promoted lung tumor growth and metastasis. Endothelial-specific overexpression of FOXF1 normalized tumor vessels and inhibited the progression of lung cancer. FOXF1 deficiency decreased Wnt/β-catenin signaling in TECs through direct transcriptional activation of Fzd4. Restoring FZD4 expression in FOXF1-deficient TECs through endothelial-specific nanoparticle delivery of Fzd4 cDNA rescued Wnt/β-catenin signaling in TECs, normalized tumor vessels and inhibited the progression of lung cancer. Altogether, FOXF1 increases tumor vessel stability, and inhibits lung cancer progression by stimulating FZD4/Wnt/β-catenin signaling in TECs. Nanoparticle delivery of FZD4 cDNA has promise for future therapies in NSCLC. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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