Abstract | BACKGROUND: METHODS:
RNA sequencing of cisplatin-resistant and -sensitive (chemoresistant and chemosensitive, respectively) ovarian cancer organoids was performed, followed by detection of the expression level of fibrillin-1 (FBN1) in organoids and clinical specimens of ovarian cancer. Subsequently, glucose metabolism, angiogenesis, and chemosensitivity were analyzed in structural glycoprotein FBN1-knockout cisplatin-resistant ovarian cancer organoids and cell lines. To gain insights into the specific functions and mechanisms of action of FBN1 in ovarian cancer, immunoprecipitation, silver nitrate staining, mass spectrometry, immunofluorescence, Western blotting, and FÓ§rster resonance energy transfer-fluorescence lifetime imaging analyses were performed, followed by in vivo assays using vertebrate model systems of nude mice and zebrafish. RESULTS: CONCLUSIONS: The FBN1/VEGFR2/STAT2 signaling axis may induce chemoresistance of ovarian cancer cells by participating in the process of glycolysis and angiogenesis. The present study suggested a novel FBN1-targeted therapy and/or combination of FBN1 inhibition and antiangiogenic drug for treating ovarian cancer.
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Authors | Ziliang Wang, Wei Chen, Ling Zuo, Midie Xu, Yong Wu, Jiami Huang, Xu Zhang, Yongheng Li, Jing Wang, Jing Chen, Husheng Wang, Huizhen Sun |
Journal | Cancer communications (London, England)
(Cancer Commun (Lond))
Vol. 42
Issue 3
Pg. 245-265
(03 2022)
ISSN: 2523-3548 [Electronic] United States |
PMID | 35234370
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center. |
Chemical References |
- Fibrillin-1
- STAT2 Transcription Factor
- STAT2 protein, human
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factor Receptor-2
- Cisplatin
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Topics |
- Animals
- Cell Line, Tumor
- Cisplatin
(pharmacology)
- Drug Resistance, Neoplasm
- Female
- Fibrillin-1
(genetics, metabolism)
- Glycolysis
- Humans
- Mice
- Mice, Knockout
- Mice, Nude
- Neovascularization, Pathologic
(drug therapy, metabolism)
- Organoids
(metabolism)
- Ovarian Neoplasms
(drug therapy, genetics)
- STAT2 Transcription Factor
(metabolism)
- Vascular Endothelial Growth Factor A
(metabolism, therapeutic use)
- Vascular Endothelial Growth Factor Receptor-2
(genetics, metabolism, therapeutic use)
- Zebrafish
(metabolism)
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