# Functional interplay between Hippo and estrogen receptor ESR1

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $412,680

## Abstract

Functional interplay between Hippo and estrogen receptor ESR1
Project Summary/Abstract
 The majority of breast cancers are estrogen receptor (ER positive and growth of ER+
cancer is dependent on ER function. Hormone therapy by inhibiting ER is most commonly used
for ER+ breast cancer treatment, however, drug resistance develops. There is strong medical
need to develop new therapy, particularly for hormone therapy resistant breast cancer. Estrogen
receptor 1 (ESR1) encodes the major form of ER and has been extensively studied for its function
as a nuclear transcription factor. However, the transcriptional regulation of ESR1 itself is less
understood. Preliminary studies from our laboratory have shown that ESR1 expression is tightly
controlled by the Hippo pathway, which is known for its role in organ size control and
tumorigenesis. Deletion of LATS1/2 kinases, core components of the Hippo pathway, abolishes
ESR1 expression and inhibits growth of ER+ breast cancer cells. We further discovered that
LATS1/2 suppress cancer cell immunogenicity. This proposal is based on our novel and exciting
observations. A major goal of this project is to reveal the molecular mechanism of ESR1
transcription regulation by the Hippo pathway and the functional significance of ESR1 in mediating
Hippo biology in breast tissue. Furthermore, we posit that LATS inhibition has two effects on ER+
breast cancer: suppression of cell growth by reducing ESR1 expression; and enhancing the
efficacy of immunotherapy by increasing cancer cell immunogenicity. The second major goal is
to provide scientific basis for targeting the LATS1/2 kinases as a novel therapy for ER+ breast
cancer.

## Key facts

- **NIH application ID:** 10795892
- **Project number:** 5R01CA268179-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jing Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $412,680
- **Award type:** 5
- **Project period:** 2022-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795892

## Citation

> US National Institutes of Health, RePORTER application 10795892, Functional interplay between Hippo and estrogen receptor ESR1 (5R01CA268179-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10795892. Licensed CC0.

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