Transcriptomics

Dataset Information

0

FOXF1 Promotes Tumor Vessel Normalization and Prevents Lung Cancer Progression through FZD4


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 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 over-expression of FOXF1 normalized tumor vessels and inhibited 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 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 a promise for future therapies in NSCLC.

ORGANISM(S): Mus musculus

PROVIDER: GSE255969 | GEO | 2024/03/09

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2016-11-17 | E-MTAB-4842 | biostudies-arrayexpress
2021-07-07 | PXD014123 | Pride
2019-12-30 | E-MTAB-6308 | biostudies-arrayexpress
2020-05-20 | E-MTAB-7458 | biostudies-arrayexpress
2020-03-07 | E-MTAB-8031 | biostudies-arrayexpress
2022-09-16 | GSE213279 | GEO
2022-09-16 | GSE213016 | GEO
2022-09-16 | GSE213017 | GEO
2023-08-15 | GSE215933 | GEO
2016-04-20 | GSE78184 | GEO