ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1.
ANGPTL4
Angiogenesis
ESM1
JAK2/STAT3 pathway
Ovarian cancer
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
11 Jan 2024
11 Jan 2024
Historique:
received:
12
07
2023
accepted:
21
12
2023
medline:
12
1
2024
pubmed:
12
1
2024
entrez:
11
1
2024
Statut:
epublish
Résumé
Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
Sections du résumé
BACKGROUND
BACKGROUND
Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated.
METHODS
METHODS
The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking.
RESULTS
RESULTS
Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis.
CONCLUSION
CONCLUSIONS
Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
Identifiants
pubmed: 38212795
doi: 10.1186/s12967-023-04819-8
pii: 10.1186/s12967-023-04819-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
46Subventions
Organisme : Natural Science Foundation of Hunan Province
ID : 2021JJ50070
Organisme : Natural Science Foundation of Hunan Province
ID : 2023JJ41066
Informations de copyright
© 2024. The Author(s).
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