# Role of cholecystokinin receptor in hepatocellular cancer

> **NIH NIH K01** · GEORGETOWN UNIVERSITY · 2023 · $162,969

## Abstract

Project Summary/ Abstract
Background: The cholecystokinin (CCK) receptor is a G-protein coupled receptor that regulates physiologic
gastrointestinal digestive functions and growth of the gastrointestinal tract. CCK receptors become
overexpressed in gastrointestinal cancers where receptor activation by the ligands, CCK on or gastrin,
stimulate cancer growth and metastases. CCK receptors have also been described as fibroblasts. When
activated, these cells produce collagen-associated proteins that lead to fibrosis associated with malignancies
and are thought to impede the penetration of therapeutic agents.
Innovation: We recently showed that a diet high in saturated fat induces the expression of hepatic CCK- B
receptors in a murine model of nonalcoholic steatohepatitis. The CCK receptor antagonist, proglumide,
reversed inflammation, fibrosis, and steatosis prevented the development of hepatocellular carcinoma in the
murine NASH model.
Long-term objectives: In this proposal, I plan to investigate the mechanisms of how CCK receptors mediate
hepatic inflammation and fibrosis and the role of CCK receptors in hepatocellular cancer.
Research Aims: In vitro studies will be performed to analyze the potential of cross-talk between CCK
receptors and chemokine receptors. The role of CCK receptors in regulating hepatic fibrosis in stellate cells will
be carried out in vitro using CRISPR technology to selectively knockout cancer cell CCK receptors and in vivo
with transgenic mice engineered to be null in the CCK-B receptor. Lastly, we will examine the novel idea of
whether liver injury and NASH induce proliferation of hepatic stem cells that express CCK-B receptors and
these stem cells are responsible for HCC.
Candidate's Goals: Are to understand the pathophysiology of CCK receptors in liver cancer development and
progression. This proposal will be completed under the guidance of an experienced mentor team that includes
accomplished tumor biologists, immunologists, and hepatology cancer researchers. To accomplish these
goals, the candidate will work with her mentors and constantly review research objectives for publication to
address candidate’s publication record and the Professional Development Office to follow a career
development plan by incorporating diverse methodologies for advancement, which includes manuscript
preparation, project management adhering to timelines, effectively managing a budget, attending and
presenting at national conferences and departmental seminars, mentoring graduate and undergraduate
students, and preparing application materials.

## Key facts

- **NIH application ID:** 10695975
- **Project number:** 5K01CA255572-03
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Martha Gay
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $162,969
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10695975

## Citation

> US National Institutes of Health, RePORTER application 10695975, Role of cholecystokinin receptor in hepatocellular cancer (5K01CA255572-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10695975. Licensed CC0.

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