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Advanced Science

Advanced Science

IF: 14.3
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Platelet-Derived Growth Factor C Facilitates Malignant Behavior of Pancreatic Ductal Adenocarcinoma by Regulating SREBP1 Mediated Lipid Metabolism

Published:3 September 2024 DOI: PMID: 39225567
Yin-Hao Shi, Zhi-De Liu, Ming-Jian Ma, Guang-Yin Zhao, Ying-Qin Zhu, Jie-Qin Wang, Yang-Yin-Hui Yu, Xi-Tai Huang, Jing-Yuan Ye, Fu-Xi Li, Xi-Yu Wang, Qiong-Cong Xu, Xiao-Yu Yin

Abstract

Lipid metabolism reprogramming stands as a fundamental hallmark of cancer cells. Unraveling the core regulators of lipid biosynthesis holds the potential to find promising therapeutic targets in pancreatic ductal adenocarcinoma (PDAC). Here, it is demonstrated that platelet-derived growth factor C (PDGFC) orchestrated lipid metabolism, thereby facilitated the malignant progression of PDAC. Expression of PDGFC is upregulated in PDAC cohorts and is corelated with a poor prognosis. Aberrantly high expression of PDGFC promoted proliferation and metastasis of PDAC both in vitro and in vivo. Mechanistically, PDGFC accelerated the malignant progression of PDAC by upregulating fatty acid accumulation through sterol regulatory element-binding protein 1 (SREBP1), a key transcription factor in lipid metabolism. Remarkably, Betulin, an inhibitor of SREBP1, demonstrated the capability to inhibit proliferation and metastasis of PDAC cell lines, along with attenuating the process of liver metastasis in vivo. Overall, the study underscores the pivotal role of PDGFC-mediated lipid metabolism in PDAC progression, suggesting PDGFC as a potential biomarker for PDAC metastasis. Targeting PDGFC-induced lipid metabolism emerges as a promising therapeutic strategy for metastatic PDAC, with the potential to improve clinical outcomes.

Substances (12)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Betulin 473-98-3 C30H50O2 538 suppliers $10.00-$1353.66
Betulin 473-98-3 C30H50O2 538 suppliers $10.00-$1353.66
Betulin 473-98-3 C30H50O2 538 suppliers $10.00-$1353.66
Betulin 473-98-3 C30H50O2 538 suppliers $10.00-$1353.66
Nile Red 7385-67-3 C20H18N2O2 362 suppliers $5.00-$945.00
Nile Red 7385-67-3 C20H18N2O2 362 suppliers $5.00-$945.00
Nile Red 7385-67-3 C20H18N2O2 362 suppliers $5.00-$945.00
Nile Red 7385-67-3 C20H18N2O2 362 suppliers $5.00-$945.00
Crenolanib 670220-88-9 C26H29N5O2 170 suppliers $24.00-$5045.00
Crenolanib 670220-88-9 C26H29N5O2 170 suppliers $24.00-$5045.00
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