# Bile Acid-Mediated IQGAP1 Regulation Drives Hepatic Tumorigenesis

> **NIH NIH F30** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $44,577

## Abstract

Project Summary/Abstract
 Hepatocellular carcinoma (HCC) is the second most lethal cancer worldwide, and its incidence is rapidly
increasing in the United States. These findings underscore the immense need to identify new therapeutic as
well as early diagnostic targets for HCC. Our laboratory previously discovered that bile acids, a family of
endogenous cholesterol metabolites synthesized in the liver, were able to activate the pro-proliferative YAP
(Yes-Associated Protein) signaling. Importantly, it was also found that this YAP activation is dependent on a
scaffolding protein IQ motif-containing GTPase Activating Protein 1 (IQGAP1). In fact, overexpression of
IQGAP1 is associated with a poor prognosis in a number of cancers including HCC. Consistent with this
hypothesis, IQGAP1 is known to regulate and integrate numerous signaling pathways, which are commonly
upregulated in cancer including ERK, YAP, mTOR, and EGFR. However, the regulation of IQGAP1 remains
largely unknown. This proposal aims to identify the regulation and role for IQGAP1 during HCC development
by determining (i) How do bile acids induce IQGAP1 expression? and (ii) What is the contribution of IQGAP1 in
promoting liver tumor development? Bile acids signal primarily through nuclear receptors to increase
transcription of target genes with farnesoid X receptor (FXR) being the major one to carry out the downstream
effects of bile acids. Our preliminary data identified that increased BAs induced Iqgap1 mRNA in vitro in a
dose-dependent manner. Interestingly, this Iqgap1 mRNA induction was mimicked when FXR was specifically
activated by GW4064 treatment, suggesting that bile acids may activate Iqgap1 expression via FXR. The first
aim of this proposal is to elucidate the BA receptor(s) and signaling pathway(s) responsible for IQGAP1. The
second aim is focused on delineating the role for IQGAP1 in liver tumor development and determining if
IQGAP1 is necessary to drive hepatic tumor promotion by bile acids. The robust diethylnitrosamine (DEN)
mouse model of chemically induced liver tumorigenesis will be used to address this aim. Successful
completion of this work will identify the mechanism for Iqgap1 regulation by bile acids and determine if
manipulating IQGAP1 expression can be an effective strategy to limit the growth of liver tumors.

## Key facts

- **NIH application ID:** 10160810
- **Project number:** 5F30CA206495-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Hanna Erickson
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,577
- **Award type:** 5
- **Project period:** 2018-05-16 → 2022-02-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160810

## Citation

> US National Institutes of Health, RePORTER application 10160810, Bile Acid-Mediated IQGAP1 Regulation Drives Hepatic Tumorigenesis (5F30CA206495-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10160810. Licensed CC0.

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