# Define the molecular mechanisms in and identify biomarkers for FAK-driven hepatocellular carcinoma

> **NIH NIH F30** · LOYOLA UNIVERSITY CHICAGO · 2024 · $47,015

## Abstract

Abstract
 Hepatocellular carcinoma (HCC) is a deadly cancer with poor prognosis and limited therapeutic options.
Biopsies are contraindicated in HCC, restricting our ability to identify unique tumor drivers and subsequent
therapeutic targets. Innovative target identification for HCC treatment is thus a critical research gap.
 Our lab has previously established focal adhesion kinase (FAK) as a driver of HCC, with 16% of HCC
patients presenting with an amplification of the PTK2 gene that encodes FAK. However, the mechanism of FAK
in HCC tumor promotion remains unknown. After treatment with a proteolysis-targeting chimera for FAK in HCC
cell lines, unbiased RNA-sequencing showed that connective tissue growth factor (CTGF) was significantly
downregulated following the pharmacological degradation of FAK. CTGF has recently been established as a
tumor promoter across several cancer types, but its role in HCC remains elusive. CTGF is secreted from cells
and can be detected in conditioned media in vitro and serum in vivo.
 Preliminary work in HCC cell lines has confirmed a relationship between FAK expression and CTGF
expression under several different conditions. CTGF expression and secretion is decreased following the
degradation of FAK; CTGF expression and secretion is increased following FAK overexpression; and basal
expression levels of FAK and CTGF show high correlation across a panel of HCC cell lines. Furthermore, the
knockdown of CTGF was found to significantly inhibit cell growth both in vitro and in vivo.
 Given this preliminary data, we hypothesize that FAK promotes CTGF expression, and CTGF in turn
promotes HCC. Furthermore, we hypothesize that serum CTGF levels can be used as a surrogate marker for
FAK expression and/or activity in HCC, indicating the utility of a FAK-targeting treatment in the clinic. We will
address these hypotheses by (1) determining the mechanism through which FAK promotes CTGF expression in
HCC, (2) evaluating the contribution of CTGF to HCC growth, and (3) determining if CTGF serum levels are
correlated to tumor FAK protein and FAK Y397 phosphorylation levels in HCC mouse models and patient
samples. This study will utilize a combination of in vitro and in vivo models as well as patient samples obtained
from clinical collaborators. Overall, this study will characterize a novel tumor-promotion pathway and elucidate a
unique predictive biomarker in HCC.

## Key facts

- **NIH application ID:** 10903278
- **Project number:** 1F30CA287907-01A1
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Claudia Rose Keating
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $47,015
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903278

## Citation

> US National Institutes of Health, RePORTER application 10903278, Define the molecular mechanisms in and identify biomarkers for FAK-driven hepatocellular carcinoma (1F30CA287907-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10903278. Licensed CC0.

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