# Role of Gastrokine 2 in pancreatic cancer development

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $40,491

## Abstract

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest adult cancers with a 5-year survival rate of
only 11% and is one of the top five leading causes of cancer-related deaths for men and women in the United
States. These dire statistics underscore the need for a better understanding of the mechanisms that promote
pancreatic cancer initiation and progression. Recent studies have begun to show that metaplastic epithelial
differentiation in pancreatic cancer can significantly impact disease progression. Our preliminary data from
ongoing studies investigating the role of cytokines IL-12/IL-23 in pancreatic cancer cell differentiation showed
that gain of aggressive epithelial to mesenchymal-like phenotype is associated with the concurrent loss of gastric
lineage genes, including Gastrokine 2 (Gkn2). Gkn2 is abundantly expressed by normal stomach epithelial cells,
plays an anti-inflammatory role in gastric epithelial homeostasis. Recently, Gkn2 and its family member Gkn1
have been shown to be de novo upregulated in metaplastic epithelial cells in pancreatic cancer. However, the
functional roles of gastrokines in pancreatic tumorigenesis remain unclear. The goals of this proposal are to
elucidate the kinetics, cellular source, and driver(s) of de novo Gkn2 expression in pancreatic neoplasia, as well
as determine the functional role of Gkn2 in pancreatic cancer development. To achieve these goals, in Aim 1,
we will determine the expression pattern and cellular identity of Gkn2-positive cells, as well as understand how
oncogenic Kras and/or Src signaling may contribute to the expression of Gkn2 in pancreatic epithelial cells. In
Aim 2, we will investigate the functional role of Gkn2 in pancreatic tumor growth, tumor cell differentiation, and
invasion. Specifically, we will utilize reversible Gkn2 knockdown systems to determine its contribution to the
growth and differentiation of Kras-transformed epithelial cells in pancreatic cancer. Our proposed research will
utilize state-of-the art models to provide an understanding of how a gastric identity gene program emerges early
in transformed pancreatic epithelium and acts as a potential impediment to the aggressive progression of cancer.

## Key facts

- **NIH application ID:** 10884874
- **Project number:** 5F31CA278589-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Whitney Jean Bell
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,491
- **Award type:** 5
- **Project period:** 2023-07-12 → 2025-07-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884874

## Citation

> US National Institutes of Health, RePORTER application 10884874, Role of Gastrokine 2 in pancreatic cancer development (5F31CA278589-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10884874. Licensed CC0.

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