Forkhead box F2/ Lysyl oxidase like 1 contribute to epithelial-mesenchymal transition and angiogenesis in thyroid cancer.
Animals
Mice
beta Catenin
/ metabolism
Cell Line, Tumor
Epithelial-Mesenchymal Transition
/ genetics
Protein-Lysine 6-Oxidase
/ genetics
Mice, Nude
Gene Expression Regulation, Neoplastic
Wnt Signaling Pathway
/ genetics
Cell Proliferation
/ genetics
Thyroid Neoplasms
/ genetics
Cell Movement
/ genetics
Angiogenesis
Forkhead box F2
Lysyl oxidase like 1
Thyroid cancer
Wnt/β-catenin
Journal
Cellular signalling
ISSN: 1873-3913
Titre abrégé: Cell Signal
Pays: England
ID NLM: 8904683
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
received:
31
07
2023
revised:
17
10
2023
accepted:
27
10
2023
medline:
4
12
2023
pubmed:
3
11
2023
entrez:
2
11
2023
Statut:
ppublish
Résumé
Bioinformatics analysis suggests an association between lysyl oxidase like 1 (LOXL1) and forkhead box F2 (FOXF2), both of which are found to be dysregulated in thyroid cancer. This study aims to elucidate their specific roles in thyroid cancer. The correlation of LOXL1 expression with thyroid cancer staging and the overall survival was analyzed. LOXL1 levels were determined in several thyroid cancer cells, and its effects on poorly differentiated BCPAP cell proliferation, colony formation, malignant phenotypes, epithelial-mesenchymal transition (EMT) progression, and angiogenesis were evaluated. The relationship between LOXL1 and FOXF2 was confirmed using Luciferase reporter and ChIP assays. The impacts of FOXF2 on LOXL1 regulation along with the Wnt/β-catenin signaling were assessed, followed by the verification of transplanted tumor in nude mice. Elevated LOXL1 expression was associated with advanced clinical staging and poorer overall survival. Reduced LOXL1 suppressed cell proliferation, colony formation, migration, invasion, EMT, and angiogenesis. FOXF2 was found to be down-regulated in thyroid cancer, acting as a transcription factor that recognizes the LOXL1 promoter and modulates its transcriptional expression. Moreover, the regulatory outcome of LOXL1 knockdown was partially reversed upon FOXF2 knockdown, including the modulation of the Wnt/β-catenin signaling and tumor growth in vivo. Our findings indicate that LOXL1 is transcriptionally regulated by FOXF2 and activates the Wnt/β-catenin to promote malignant phenotypes, EMT progression, and angiogenesis in BCPAP cells.
Sections du résumé
BACKGROUND
BACKGROUND
Bioinformatics analysis suggests an association between lysyl oxidase like 1 (LOXL1) and forkhead box F2 (FOXF2), both of which are found to be dysregulated in thyroid cancer. This study aims to elucidate their specific roles in thyroid cancer.
METHODS
METHODS
The correlation of LOXL1 expression with thyroid cancer staging and the overall survival was analyzed. LOXL1 levels were determined in several thyroid cancer cells, and its effects on poorly differentiated BCPAP cell proliferation, colony formation, malignant phenotypes, epithelial-mesenchymal transition (EMT) progression, and angiogenesis were evaluated. The relationship between LOXL1 and FOXF2 was confirmed using Luciferase reporter and ChIP assays. The impacts of FOXF2 on LOXL1 regulation along with the Wnt/β-catenin signaling were assessed, followed by the verification of transplanted tumor in nude mice.
RESULTS
RESULTS
Elevated LOXL1 expression was associated with advanced clinical staging and poorer overall survival. Reduced LOXL1 suppressed cell proliferation, colony formation, migration, invasion, EMT, and angiogenesis. FOXF2 was found to be down-regulated in thyroid cancer, acting as a transcription factor that recognizes the LOXL1 promoter and modulates its transcriptional expression. Moreover, the regulatory outcome of LOXL1 knockdown was partially reversed upon FOXF2 knockdown, including the modulation of the Wnt/β-catenin signaling and tumor growth in vivo.
CONCLUSION
CONCLUSIONS
Our findings indicate that LOXL1 is transcriptionally regulated by FOXF2 and activates the Wnt/β-catenin to promote malignant phenotypes, EMT progression, and angiogenesis in BCPAP cells.
Identifiants
pubmed: 37918464
pii: S0898-6568(23)00371-6
doi: 10.1016/j.cellsig.2023.110956
pii:
doi:
Substances chimiques
beta Catenin
0
Protein-Lysine 6-Oxidase
EC 1.4.3.13
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
110956Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All authors have no conflicts of interest to declare.