# Vascular regulation of fatty acid transport in metastatic tumor outgrowth

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $480,397

## Abstract

Project Summary
Tumor metastasis requires supportive microenvironment for outgrowth of disseminated tumor
cells. The switch of metastatic cells from dormant to proliferative state needs nutrients for
energetics and biomass production. Although metabolic regulation of tumor metastasis is not well-
established, recent studies demonstrated the importance of fatty acid (FA) uptake and metabolism
in tumor cells that drives metastatic tumor outgrowth. However, it is unclear how FA pools in the
tumor microenvironment is regulated. The vascular system plays a crucial role in supplying
nutrients. This application investigates how vascular endothelial cells regulate FA transportation
and utilization in metastatic tumor outgrowth. We discovered that loss of Raptor/mTORC1, but
not Rictor/mTORC2, in vascular endothelium inhibits metastatic tumor outgrowth in lung.
Raptor/mTORC1 deficiency led to reduced long chain fatty acid (LCFA) and polyunsaturated fatty
acid (PUFA) in endothelial cells (EC), decreased expression of membrane proteins that mediate
FA transport, reduced FA uptake and transport across endothelium, and decreased lipid droplets
in metastatic tumors. Based on these preliminary data, we propose a model in which mTORC1
activities in vascular endothelial cells stimulate transendothelial FA transport, leading to enhanced
FA utilization in tumor cells and metastatic outgrowth. To test this hypothesis, we will investigate
downstream mechanisms by which vascular mTORC1 regulates transport of fatty acids across
the endothelium (Aim 1), upper-stream factors that stimulate the FA transport (Aim 2), and
determine if selectively blocking endothelial mTORC1 will suppress metastatic outgrowth and
improve chemo- and immunotherapy against metastasis (Aim 3). The proposed work is innovative
in its concept that mTORC1 regulates tumor blood vessel transportation of fatty acids. It also
utilizes several state-of-the-art technologies, including a metabolomics screen, MALDI-imaging
mass spectrometry for lipid/FA detection on tumor section in situ, a breast cancer PDX model,
and several new conditional mouse models. These studies would set the stage for future
development of strategies selectively targeting endothelial mTORC1 or fatty acid transportation
to improve anti-cancer therapy.

## Key facts

- **NIH application ID:** 10895442
- **Project number:** 5R01CA271176-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jin Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $480,397
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895442

## Citation

> US National Institutes of Health, RePORTER application 10895442, Vascular regulation of fatty acid transport in metastatic tumor outgrowth (5R01CA271176-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10895442. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*