# The role of lipids in melanoma progression via induction of ER stress and lipid droplet formation

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $51,752

## Abstract

PROJECT SUMMARY
Melanoma is the most lethal skin cancer, and progression to metastatic disease leads to severe reduction in
patient survival. The tumor microenvironment (TME) plays a significant role in supporting tumor growth and
promoting cancer metastasis. Our laboratory recently discovered that TME adipocytes can directly transfer fatty
acids into melanoma cells and promote invasion. Fatty acids can serve as a multipurpose building block to benefit
cells, but excess fatty acids can also trigger endoplasmic reticulum (ER) stress. Growing evidence suggests that
ER stress can induce cancer cell invasion and survival programs leading to metastasis, but the mechanism by
which this occurs remains unclear. Our preliminary data suggests that adipocyte-derived lipids induce ER stress
which promotes invasion gene programs. In Aim 1, we will investigate the role of lipid induced ER stress in
metastasis. We will mechanistically dissect which ER stress pathways are induced by adipocyte derived lipids,
and characterize how ER stress upregulates canonical melanoma invasion genes to facilitate metastasis. We
hypothesize that lipids induce IRE and PERK, two branches of ER stress previously linked with cancer
metastasis, and promotes melanoma invasion through AXL, a potential melanoma invasion gene. While ER
stress can upregulate cell survival programs that can benefit cancer, persistent ER stress leads to cell death. To
combat ER stress due to lipid overload, cells can form lipid droplets (LD) which are cytosolic organelles
containing a neutral lipid core. LDs can protect cells from toxic side effects of lipids and act a regulated source
of lipid accessibility. In Aim 2, we will examine how LDs protect cancer cells against lipid mediated stress.
We will investigate the mechanism by which LDs can alleviate ER stress and determine their role in promoting
cancer metastasis. We hypothesize that LDs reduce ER stress by sequestering lipids out of the ER lumen and
compartmentalize lipids to be used as fuel for cancer progression. We will utilize both human and zebrafish
melanoma cells to generate genetic perturbations within ER stress and LD formation pathways in order to
understand how these two mechanisms support melanoma progression. We will perform tumor transplants in
zebrafish and apply computational image analysis to investigate the role of these pathways in promoting
metastasis in vivo. These combined approaches will lead to novel insights into ER stress and LD formation as
mechanisms of cancer metastasis, which can identify new strategies to block melanoma progression.

## Key facts

- **NIH application ID:** 10431879
- **Project number:** 5F30CA254152-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Dianne Lumaquin
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10431879

## Citation

> US National Institutes of Health, RePORTER application 10431879, The role of lipids in melanoma progression via induction of ER stress and lipid droplet formation (5F30CA254152-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10431879. Licensed CC0.

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