# Elucidating the Function of LRP1 in APOE-mediated Suppression of Melanoma Metastasis

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

## Abstract

PROJECT SUMMARY/ABSTRACT
Metastatic melanoma is the cause of over 80% of skin cancer deaths. Previous work in our lab interrogating the
molecular differences between highly and poorly metastatic melanoma cells revealed that expression of the
secreted protein apolipoprotein E (APOE) is repressed in aggressive melanomas through microRNA targeting.
Rescuing APOE expression through genetic and pharmacologic approaches suppresses metastatic phenotypes
and prolongs survival in melanoma animal models. Suppression of the invasion phenotype in particular was
found to be mediated by low-density lipoprotein receptor-related protein 1 (LRP1), an APOE receptor present on
the melanoma cell surface. However, the mechanisms by which LRP1 cooperates with APOE to facilitate
inhibition of melanoma invasion remain uncharacterized. This proposal seeks to elucidate the molecular
alterations initiated by this APOE-LRP1 interaction that result in loss of melanoma invasive capacity. Based on
literature evidence and preliminary data, I hypothesize that APOE inhibits melanoma invasiveness by activating
an LRP1 signaling axis. This hypothesis will be tested through the following two aims: In Aim 1, I will fully
characterize the functional consequences of LRP1 loss on APOE-mediated metastasis suppression by
developing LRP1 genetic knockouts in melanoma cell lines and performing metastasis assays as well as
transcriptomic analysis. In Aim 2, I will explore the role of LRP1 intracellular signaling as a potential suppressive
mechanism downstream of APOE binding by developing LRP1 signaling mutants in melanoma cell lines and in
a genetic mouse melanoma model. Successful completion of these studies will uncover a novel, therapeutically
targetable signaling pathway that regulates melanoma metastasis and will further our understanding of the
influences of APOE and LRP1 on cancer progression. Training will be completed in the laboratory of Dr. Sohail
Tavazoie and the highly collaborative environments of The Rockefeller University and the Tri-Institutional MD-
PhD Program, and will be centered on my goal of becoming an independent physician-scientist.

## Key facts

- **NIH application ID:** 10329909
- **Project number:** 5F30CA257226-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Nneoma Adaku
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2021-01-11 → 2025-01-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10329909

## Citation

> US National Institutes of Health, RePORTER application 10329909, Elucidating the Function of LRP1 in APOE-mediated Suppression of Melanoma Metastasis (5F30CA257226-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10329909. Licensed CC0.

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