# Regulation of ER-beta Signaling in Carcinogenesis

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2021 · $484,266

## Abstract

Estrogen receptor (ER)β exhibits an antitumor activity in multiple cancer types in both tumor-intrinsic
and -extrinsic manners. However, little is known as to how such activity can be harnessed with high efficacy
and precision, nor is it clear which host cell type(s) mediates the tumor-extrinsic function of ERβ. These major
knowledge gaps hamper efforts to unleash ERβ antitumor activity for cancer therapies. We recently discovered
a phosphotyrosine-dependent signaling axis that controls ERβ antitumor activity. Furthermore, using a novel
knockin mouse model, we found that this phosphotyrosine switch plays a significant role in host cells to
promote antitumor immunity. Our central hypothesis is that this ERβ-centered signaling axis provides a
previously unrecognized molecular handle for mobilizing tumor-extrinsic antitumor activity of ERβ in
immune cells. Armed with genetic and pharmacological tools that both specifically target this signaling circuit,
our multi-PI team will validate this novel hypothesis through three Specific Aims. First, we will identify the exact
immune cell type(s) that mediates tumor-extrinsic ERβ signaling in antitumor immunity (Aim 1). We will then
delineate the upstream regulators and downstream target genes of ERβ signaling in immune cells (Aim 2).
Lastly, we will assess the anticancer therapeutic potential of targeting this ERβ signaling axis to boost current
cancer immunotherapies. Findings from these experiments will shed light on a previously under-appreciated
signaling pathway governing tumor-immune cell interactions in the tumor microenvironment. As
immunotherapies are becoming an important pillar of cancer therapy, the proposed study will help improve
clinical outcomes and efficacy of immunotherapy for larger numbers of cancer patients.

## Key facts

- **NIH application ID:** 10092967
- **Project number:** 5R01CA206529-05
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Tyler J. Curiel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $484,266
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10092967

## Citation

> US National Institutes of Health, RePORTER application 10092967, Regulation of ER-beta Signaling in Carcinogenesis (5R01CA206529-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10092967. Licensed CC0.

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