# Role of protein mediate fatty acid uptake in liver cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $510,306

## Abstract

Project Summary
While less frequent than hepatocellular carcinomas (HCC), intrahepatic carcinomas (ICC) are a lethal condition
with rising incidence rate and, currently, few treatment options. We recently demonstrate that fatty acid
synthase (FASN) activity is required for efficient growth of HCC but not for ICC. Given the essential role of fatty
acids for membrane synthesis, signaling molecules, and energy substrates this led us to hypothesize that ICC
relies on the uptake of exogenous free fatty acids (FFA). Importantly, cell surface molecules have been
identified that that are required for efficient uptake of free fatty acids from the circulation. As these molecules
have already been shown to be drugable targets, in principle, they might offer new treatment approaches for
this deadly disease. Our central hypothesis that protein mediated fatty acid uptake is required for ICC
growth in vivo to generate as yet unknown signals that cannot be provided via de novo synthesis of
fatty acids. This hypothesis is supported by key preliminary data showing that ICC, but not HCC, express the
classical hepatic fatty acid transporters Slc27a2 and Slc27a5 and that ICC isolated primary tumor cells display
a robust uptake of exogenous fatty acids. Moreover, using novel assay to determine changes in fatty acid
uptake during tumor growth in vivo, we were able to show higher exogenous long-chain fatty acid uptake by
ICC tumors compared to an HCC model. Importantly, loss of Slc27a5 diminishes ICC growth in experimental
tumor models in spite of FASN expression. Preliminary lipidomics studies comparing lipid compositions in
normal and end-stage ICC and HCC models showed significantly higher fatty acid levels in ICC tumor laden
livers compared to HCC and for some lipid species even surpassing concentrations found in normal liver.
These studies also have begun to shed light on the metabolic fate of the exogenous fatty acids, which might
lead to identification of key signals uniquely provided by exogenous fatty acids. Here, using mouse model
systems and human ICC PDX, we will determine when and to what extend exogenous FFA uptake is required
for the growth of ICC, how it is facilitated, and what unique roles Slc27 driven FFA uptake provides.

## Key facts

- **NIH application ID:** 9978744
- **Project number:** 5R01CA221916-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Daniel Nomura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $510,306
- **Award type:** 5
- **Project period:** 2018-08-17 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978744

## Citation

> US National Institutes of Health, RePORTER application 9978744, Role of protein mediate fatty acid uptake in liver cancer (5R01CA221916-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9978744. Licensed CC0.

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