Activation of platelet-derived growth factor receptors regulate connective tissue growth factor protein levels via the AKT pathway in malignant mesothelioma cells

Activation of platelet-derived growth factor receptors regulate connective tissue growth factor protein levels via the AKT pathway in malignant mesothelioma cells

The incidence of malignant mesothelioma (MM), a disease linked to refractory asbestos exposure, continues to increase globally, and remains largely resistant to various treatments. Our previous studies have identified a strong correlation between connective tissue growth factor (CTGF) protein expres...

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Bibliographic Details
Published in:Journal of biochemistry (Tokyo)
Main Authors: Suehiro, Tomoya, Ahmad, Khoja Mouhand, Hoang, Nguyen Truong Duc, Xu, Bingwen, Komatsu, Honoka, Kurachi, Komei, Nikawa, Hiroki, Mine, Yuichi, Matsuki, Tohru, Asano, Katsura, Fujii, Makiko
Format: Journal Article
Language:English
Published: England 23-10-2024
Subjects:
4E-BP1
AKT-mTOR pathway
malignant mesothelioma
PDGF
CTGF
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Summary:The incidence of malignant mesothelioma (MM), a disease linked to refractory asbestos exposure, continues to increase globally, and remains largely resistant to various treatments. Our previous studies have identified a strong correlation between connective tissue growth factor (CTGF) protein expression and MM malignancy, underscoring the importance of understanding CTGF regulation in MM cells. In this study, we demonstrate for the first time that stimulation with platelet-derived growth factor receptor (PDGFR) ligand, PDGF-BB, increases CTGF protein expression levels without affecting CTGF mRNA levels. Inhibition of PDGFR resulted in a reduction of CTGF protein expression, indicating that PDGFR activation is essential in regulating CTGF protein expression in MM cells. PDGF-BB also activated the protein kinase B (AKT) pathway, and inhibition of AKT phosphorylation abolished the PDGFR-induced CTGF protein expression, suggesting that PDGFR acts upstream of CTGF via the AKT pathway. This reinforces the role of CTGF protein as a key regulator of MM malignancy. Additionally, PDGFR activation led to the phosphorylation of mTOR and 4E-BP1, critical regulators of protein synthesis downstream of AKT, suggesting that PDGFR controls CTGF protein expression through the regulation of CTGF mRNA translation.
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content type line 23
ISSN:0021-924X
1756-2651
1756-2651
DOI:10.1093/jb/mvae068