# Mechanisms of lipid droplet trafficking in hepatocellular carcinoma

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $170,433

## Abstract

Project Summary/Abstract
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and fourth
leading cause of cancer deaths worldwide. The incidence of HCC is rising as key risk factors
including obesity and heavy alcohol consumption are accelerating at rates greater than ever
before. These risk factors drive hepatic steatosis and steatohepatitis, marked by the extreme
accumulation of lipid droplets (LDs) in hepatocytes, leading to cirrhosis and HCC. While
lipid synthesis a well-described phenotype in HCC, the role of LDs in propagating tumor
formation and growth is poorly understood. Preliminary data from our laboratory suggests that
the small GTPase Rab5 localizes to LDs and plays a critical role in trafficking to the
lysosome, where LDs are catabolized by lysosomal acid lipase (LAL). Moreover, both Rab5
and LAL expression are increased in HCC tumors, consistent with cell biological studies
showing elevated lipophagy in HCC cell lines vs normal hepatocytes. These data support
the hypothesis that Rab5-LD interaction drives HCC tumor growth via lysosomal catabolism.
In Aim 1, we will determine the mechanisms of Rab5 binding to LDs in HCC, and how this
interaction impacts cancer cell energetics and proliferation. In Aim 2, we will determine the
impact of Rab5-mediated lipophagy on HCC tumor growth in vivo using a sleeping beauty
transposon transposase (SBTT) mouse model in which oncogenes are delivered to hepatocytes
via hydrodynamic tail vein injection (HTVI). The results gained from the proposed research will
provide a mechanistic understanding of lipid droplet trafficking and catabolism in
hepatocellular carcinoma progression. Moreover, this research will aid in future development of
larger research project grant applications.

## Key facts

- **NIH application ID:** 10854797
- **Project number:** 5R21CA279878-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Micah Schott
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $170,433
- **Award type:** 5
- **Project period:** 2023-06-02 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854797

## Citation

> US National Institutes of Health, RePORTER application 10854797, Mechanisms of lipid droplet trafficking in hepatocellular carcinoma (5R21CA279878-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10854797. Licensed CC0.

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