Inhibition of fatty acid binding protein suppresses pancreatic cancer progression and metastasis Article Swipe
Shuhei Shinoda
,
Naohiko Nakamura
,
Kazuho Inoko
,
Mizuho Sato‐Dahlman
,
Steven Carmella
,
Stephen S. Hecht
,
David Bernlohr
,
Sayeed Ikramuddin
,
Masato Yamamoto
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-025-11271-9
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-025-11271-9
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.
Related Topics
Concepts
Metastasis
Cancer research
Pancreatic cancer
Cancer
In vivo
Fatty acid-binding protein
Epithelial–mesenchymal transition
Tumor progression
Medicine
Biology
Internal medicine
Biotechnology
Biochemistry
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41598-025-11271-9
- OA Status
- gold
- Cited By
- 1
- References
- 46
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412522260
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412522260Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41598-025-11271-9Digital Object Identifier
- Title
-
Inhibition of fatty acid binding protein suppresses pancreatic cancer progression and metastasisWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
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2025-07-18Full publication date if available
- Authors
-
Shuhei Shinoda, Naohiko Nakamura, Kazuho Inoko, Mizuho Sato‐Dahlman, Steven Carmella, Stephen S. Hecht, David Bernlohr, Sayeed Ikramuddin, Masato YamamotoList of authors in order
- Landing page
-
https://doi.org/10.1038/s41598-025-11271-9Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1038/s41598-025-11271-9Direct OA link when available
- Concepts
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Metastasis, Cancer research, Pancreatic cancer, Cancer, In vivo, Fatty acid-binding protein, Epithelial–mesenchymal transition, Tumor progression, Medicine, Biology, Internal medicine, Biotechnology, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
- References (count)
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46Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.for | 6, 50 |
| abstract_inverted_index.the | 27, 36, 45, 55, 172 |
| abstract_inverted_index.was | 133 |
| abstract_inverted_index.(KPC | 78 |
| abstract_inverted_index.PDAC | 41, 51, 82, 194 |
| abstract_inverted_index.acid | 12 |
| abstract_inverted_index.also | 134 |
| abstract_inverted_index.both | 107 |
| abstract_inverted_index.cell | 74, 83 |
| abstract_inverted_index.into | 35 |
| abstract_inverted_index.mice | 64 |
| abstract_inverted_index.null | 63 |
| abstract_inverted_index.risk | 4 |
| abstract_inverted_index.role | 37 |
| abstract_inverted_index.that | 96 |
| abstract_inverted_index.were | 97 |
| abstract_inverted_index.with | 99, 112, 120 |
| abstract_inverted_index.FABP4 | 39, 48, 59, 62, 66, 85, 108, 186 |
| abstract_inverted_index.Fatty | 11 |
| abstract_inverted_index.Human | 130 |
| abstract_inverted_index.PDAC. | 177 |
| abstract_inverted_index.These | 178 |
| abstract_inverted_index.ZEB1. | 104, 129 |
| abstract_inverted_index.human | 81 |
| abstract_inverted_index.known | 3 |
| abstract_inverted_index.liver | 157, 167 |
| abstract_inverted_index.mice. | 155 |
| abstract_inverted_index.mouse | 77, 159 |
| abstract_inverted_index.obese | 22 |
| abstract_inverted_index.tumor | 118, 146 |
| abstract_inverted_index.using | 61 |
| abstract_inverted_index.value | 184 |
| abstract_inverted_index.vivo, | 106 |
| abstract_inverted_index.which | 148 |
| abstract_inverted_index.(EMT), | 91 |
| abstract_inverted_index.cancer | 93 |
| abstract_inverted_index.cells) | 79 |
| abstract_inverted_index.ductal | 8 |
| abstract_inverted_index.factor | 5, 103 |
| abstract_inverted_index.growth | 119, 132, 147, 165 |
| abstract_inverted_index.higher | 18 |
| abstract_inverted_index.lines. | 84 |
| abstract_inverted_index.linked | 25 |
| abstract_inverted_index.model, | 142, 160 |
| abstract_inverted_index.option | 192 |
| abstract_inverted_index.plasma | 20 |
| abstract_inverted_index.vitro, | 70 |
| abstract_inverted_index.(FABP4) | 16 |
| abstract_inverted_index.(PDAC). | 10 |
| abstract_inverted_index.Obesity | 0 |
| abstract_inverted_index.binding | 13 |
| abstract_inverted_index.distant | 150 |
| abstract_inverted_index.markers | 95 |
| abstract_inverted_index.protein | 14 |
| abstract_inverted_index.provide | 33 |
| abstract_inverted_index.HTS01037 | 113, 137, 143, 161, 170 |
| abstract_inverted_index.cancers. | 31 |
| abstract_inverted_index.critical | 190 |
| abstract_inverted_index.efficacy | 173 |
| abstract_inverted_index.enhanced | 171 |
| abstract_inverted_index.findings | 179 |
| abstract_inverted_index.improved | 149 |
| abstract_inverted_index.indicate | 180 |
| abstract_inverted_index.insights | 34 |
| abstract_inverted_index.invasive | 87 |
| abstract_inverted_index.knockout | 109 |
| abstract_inverted_index.potency, | 88 |
| abstract_inverted_index.promoted | 86 |
| abstract_inverted_index.stemness | 94, 125 |
| abstract_inverted_index.HTS010137 | 71 |
| abstract_inverted_index.Moreover, | 169 |
| abstract_inverted_index.determine | 44 |
| abstract_inverted_index.inhibited | 135 |
| abstract_inverted_index.inhibitor | 49, 67, 187 |
| abstract_inverted_index.mechanism | 57 |
| abstract_inverted_index.patients, | 23 |
| abstract_inverted_index.patients. | 195 |
| abstract_inverted_index.potential | 46 |
| abstract_inverted_index.promising | 182 |
| abstract_inverted_index.reduction | 121 |
| abstract_inverted_index.survivals | 153 |
| abstract_inverted_index.syngeneic | 115 |
| abstract_inverted_index.viability | 75 |
| abstract_inverted_index.xenograft | 131 |
| abstract_inverted_index.Pancreatic | 7 |
| abstract_inverted_index.anticancer | 56 |
| abstract_inverted_index.associated | 98 |
| abstract_inverted_index.attenuated | 162 |
| abstract_inverted_index.elucidated | 54 |
| abstract_inverted_index.inhibition | 60, 111 |
| abstract_inverted_index.metastases | 151 |
| abstract_inverted_index.metastasis | 158 |
| abstract_inverted_index.orthotopic | 141 |
| abstract_inverted_index.suppressed | 72, 114, 145 |
| abstract_inverted_index.transition | 90 |
| abstract_inverted_index.treatment, | 52 |
| abstract_inverted_index.treatment. | 138 |
| abstract_inverted_index.(HTS01037). | 68 |
| abstract_inverted_index.development | 163 |
| abstract_inverted_index.gemcitabine | 175 |
| abstract_inverted_index.metastases. | 168 |
| abstract_inverted_index.progression | 28, 42 |
| abstract_inverted_index.therapeutic | 191 |
| abstract_inverted_index.subcutaneous | 117 |
| abstract_inverted_index.FABP4-induced | 73 |
| abstract_inverted_index.significantly | 144 |
| abstract_inverted_index.transcription | 102 |
| abstract_inverted_index.translational | 183 |
| abstract_inverted_index.up-regulation | 100 |
| abstract_inverted_index.adenocarcinoma | 9 |
| abstract_inverted_index.down-regulation | 127 |
| abstract_inverted_index.obesity-related | 30 |
| abstract_inverted_index.epithelial-mesenchymal | 89 |
| cited_by_percentile_year.max | 95 |
| cited_by_percentile_year.min | 91 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 9 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8399999737739563 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.85527548 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |