# Investigating the Role of Adipocyte Lipolysis in Melanoma Progression

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $47,269

## Abstract

PROJECT SUMMARY
Melanoma is the most lethal skin cancer and there remains a need to develop new therapies for patients with
disseminated disease. By identifying the communication strategies cancer depends on to survive, the tumor
microenvironment (TME) can serve as a fruitful area to identify new therapeutic targets. Melanoma cells
interact with adipocytes within subcutaneous fat, but the consequences of this interaction is poorly understood.
Our laboratory recently discovered that melanoma cells acquire lipids from stromal adipocytes and that this
leads to increased melanoma proliferation and invasion. Lipid release from adipocytes is regulated by the
breakdown of triglycerides into free fatty acids, a process known as lipolysis. The ability of cancer cells to
induce adipocyte lipolysis has been observed, but the mechanism by which this occurs and the consequences
for cancer progression remains unclear. Our preliminary data support that melanoma cells induce adipocyte
lipolysis through a secreted factor. In AIM 1, we will investigate the mechanism of melanoma-induced
adipocyte lipolysis using human melanoma cell lines and adipocytes in a co-culture system. We will
first identify which signaling pathways are involved and then target candidate molecules that are known to
mediate lipolysis through that pathway. As a byproduct of melanin synthesis, melanoma cells secrete
catecholamines, which are the primary physiologic drivers of lipolysis. Therefore, we hypothesize that
melanoma cells induce adipocyte lipolysis through secreted catecholamines. We will investigate the
relationship between pigmentation in melanoma and adipocyte lipolysis to understand how differentiation
programs influence interactions with the TME. In AIM2, we will examine the functional consequences of
adipocyte lipolysis on melanoma progression using the zebrafish as an in vivo model. Adipose
triglyceride lipase (ATGL) is the rate-limiting enzyme for lipolysis and has been shown to be required for
cancer-induced adipocyte lipolysis. We will create an adipocyte-restricted ATGL knockout in zebrafish, which
offers the advantages of rapid transgenesis and high resolution imaging of cell-cell interactions in the TME. We
will use this new in vivo model to determine the role of adipocyte lipolysis in melanoma initiation and
metastasis. We hypothesize that blocking adipocyte lipolysis will decrease melanoma initiation and metastasis
by cutting off access to extracellular lipids and creating an unfavorable microenvironment. By investigating the
role of melanoma-induced adipocyte lipolysis, this proposal seeks to understand the contribution of adipocytes
to melanoma progression and identify novel approaches to target the tumor microenvironment.
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## Key facts

- **NIH application ID:** 9834682
- **Project number:** 5F30CA236442-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Joshua M. Weiss
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $47,269
- **Award type:** 5
- **Project period:** 2018-12-04 → 2022-07-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834682

## Citation

> US National Institutes of Health, RePORTER application 9834682, Investigating the Role of Adipocyte Lipolysis in Melanoma Progression (5F30CA236442-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9834682. Licensed CC0.

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