# A novel signaling mechanism for LRP5

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $535,605

## Abstract

Project Summary / Abstract:
Cancer is a leading cause of death, but recent emergence of immunotherapies including the immune
checkpoint inhibitors has offered promising new cancer treatment options. It is also evident that tumor
immunity is highly complex and incompletely understood. The better understanding of tumor immune
regulation may lead to identification of additional targets for cancer immunomodulatory therapy. In this study
we will investigate the mechanism by which the cell surface receptor protein LRP5 regulates NK cell activities
and tumor immunity. In our preliminary studies, we found that loss of LRP5 led to increased activation of NK
cells independently of β-catenin stabilization despite LRP5 is involved in β-catenin regulation in other cells.
Thus, we hypothesize that LRP5 regulates NK activation via previously uncharacterized mechanisms.
Because genetic inactivation of LRP5 in NK cells suppresses tumor progression accompanied with enhanced
NK activities in mice, this new mechanism is potentially of important clinical implications. Our preliminary
results suggest that LRP5 may function as a fatty acid transporter leading to regulation of mTROC1 activity. In
this application, we will carry out comprehensive in vitro and in vivo investigations to characterize this new
mechanism for LRP5 and to determine the roles of this new mechanism in NK biology and tumor surveillance.

## Key facts

- **NIH application ID:** 10706591
- **Project number:** 5R01CA274735-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Dianqing Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $535,605
- **Award type:** 5
- **Project period:** 2022-09-19 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10706591

## Citation

> US National Institutes of Health, RePORTER application 10706591, A novel signaling mechanism for LRP5 (5R01CA274735-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10706591. Licensed CC0.

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