# Engrailed-1 and Epigenetic Vulnerabilities in Metastatic Pancreatic Cancer

> **NIH NIH R37** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $355,328

## Abstract

Project Summary/Abstract
Pancreatic cancer is the most deadly disease in human malignancies and effective treatment
options are limited. Here, we hypothesize that Engrailed-1 (EN1), a neuro-development
transcription factor, plays a critical role in pancreatic cancer progression and metastasis via
epigenetic mechanism of gene regulation. EN1 is a homeo-domain transcription factor, acting as
a transcriptional repressor via recruiting transcriptional repressive complexes. Our preliminary
data show that EN1 is highly expressed in metastasis-derived organoids and metastatic lesions
of pancreatic cancer mouse model. In addition, EN1 expression is associated with poor prognosis
and the squamous molecular subtype of pancreatic cancer. Here, we find that EN1 expression
endows aggressive characteristics to pancreatic cancer cells and induces the squamous-PDA
identity gene signature. Our data strongly suggest that EN1-mediated epigenetic alterations
create a new vulnerability for metastatic pancreatic cancer. Therefore, it is critical to identify the
underlying molecular mechanism by which EN1 regulates pancreatic epigenome and contributes
to PDA progression and metastasis. To address this, we will employ multi-orthogonal approaches
to understand the precise role of EN1 in PDA progression. Here, we propose 1) to determine the
role of EN1 in the pancreatic cancer epigenome, and 2) to determine the role of EN1 in pancreatic
cancer progression. The proposed study will provide a new insight how EN1-mediated epigenetic
alterations impact on aggressive traits of pancreatic cancer. This may open novel avenues for the
treatment of pancreatic cancer.

## Key facts

- **NIH application ID:** 10368153
- **Project number:** 5R37CA249007-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Chang-il Hwang
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $355,328
- **Award type:** 5
- **Project period:** 2021-03-08 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368153

## Citation

> US National Institutes of Health, RePORTER application 10368153, Engrailed-1 and Epigenetic Vulnerabilities in Metastatic Pancreatic Cancer (5R37CA249007-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10368153. Licensed CC0.

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