# Wnt/beta-catenin signaling in early-onset colorectal cancer

> **NIH NIH R03** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2024 · $83,000

## Abstract

PROJECT SUMMARY
Colorectal cancer (CRC) remains the third leading cause of cancer related deaths in the US. Although the over-
all incidence is declining, the incidence in the younger population has been steadily increasing over the past
thirty years. While a western diet and a sedentary lifestyle are among contributing environmental factors to early
onset colorectal cancer (EOCRC; as defined in individuals <50 years old), genetic research has also implicated
the Wnt/ß-catenin signaling pathway as a driver of EOCRC. Mutations in the adenomatous polyposis coli (APC)
gene, which is a tumor suppressor and encodes a negative regulatory protein of the pathway, are highly prevalent
in spontaneous CRC. These mutations drive an oncogenic gene expression program controlled by the ß-catenin
transcriptional co-regulator. APC mutations, and other regulators of Wnt/ß-catenin signaling, are also found in
EOCRC tumor samples, but the role of deregulated Wnt/ß-catenin signaling in EOCRC is not understood. The
goals of this proposal are to elucidate critical downstream Wnt/ß-catenin gene targets and to identify novel Wnt-
pathway modulators that drive EOCRC. In Aim 1, we will use RNA-seq to define differential gene expression
signatures in patient-matched colonic segments and tumors. We will focus on known downstream target genes
of Wnt/ß-catenin signaling and test their role(s) in driving EOCRC using human-derived tumoroids. In Aim 2, we
will use a CRISPR/Cas9 knockout screen to identify novel proteins that negatively regulate Wnt/ß-catenin
signaling in human colonic organoid cultures derived from EOCRC patients. This work will identify novel drivers
of EOCRC which is needed to better understand disease pathogenesis and to reveal new avenues for potential
therapeutic intervention.

## Key facts

- **NIH application ID:** 10820415
- **Project number:** 5R03CA279861-02
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Gregory S. Yochum
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $83,000
- **Award type:** 5
- **Project period:** 2023-04-04 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820415

## Citation

> US National Institutes of Health, RePORTER application 10820415, Wnt/beta-catenin signaling in early-onset colorectal cancer (5R03CA279861-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10820415. Licensed CC0.

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