Inhibition of fatty acid binding protein suppresses pancreatic cancer progression and metastasis

Inhibition of fatty acid binding protein suppresses pancreatic cancer progression and metastasis

Abstract Obesity is a known risk factor for Pancreatic ductal adenocarcinoma (PDAC). Fatty acid binding protein 4 (FABP4) is higher in plasma of obese patients, and linked to the progression of obesity-related cancers. To provide insights into the role of FABP4 in PDAC progression and determine the...

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Bibliographic Details
Main Authors: Shuhei Shinoda, Naohiko Nakamura, Kazuho Inoko, Mizuho Sato-Dahlman, Steven Carmella, Stephen Hecht, David A Bernlohr, Sayeed Ikramuddin, Masato Yamamoto
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
Pancreatic ductal adenocarcinoma
Fatty acid binding protein 4
Metastasis
Obesity
Online Access:https://doi.org/10.1038/s41598-025-11271-9
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Summary:Abstract Obesity is a known risk factor for Pancreatic ductal adenocarcinoma (PDAC). Fatty acid binding protein 4 (FABP4) is higher in plasma of obese patients, and linked to the progression of obesity-related cancers. To provide insights into the role of FABP4 in PDAC progression and determine the potential of FABP4 inhibitor for PDAC treatment, we elucidated the anticancer mechanism of FABP4 inhibition using FABP4 null mice and FABP4 inhibitor (HTS01037). In vitro, HTS010137 suppressed FABP4-induced cell viability in mouse (KPC cells) and human PDAC cell lines. FABP4 promoted invasive potency, epithelial–mesenchymal transition (EMT), and cancer stemness markers that were associated with up-regulation of transcription factor ZEB1. In vivo, both FABP4 knockout and inhibition with HTS01037 suppressed syngeneic KPC subcutaneous tumor growth with reduction of EMT and stemness and down-regulation of ZEB1. Human xenograft growth was also inhibited by HTS01037 treatment. In an orthotopic model, HTS01037 significantly suppressed tumor growth which improved distant metastases and survivals in mice. In liver metastasis mouse model, HTS01037 attenuated development and growth of liver metastases. Moreover, HTS01037 enhanced the efficacy of gemcitabine to PDAC. These findings indicate a promising translational value of FABP4 inhibitor as a critical therapeutic option in PDAC patients.
ISSN:2045-2322

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