# Nuclear AXIN2 and Colorectal Cancer

> **NIH NIH R03** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $74,211

## Abstract

PROJECT SUMMARY
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer-
related deaths in the United States. Mutations in components of the Wnt/β-catenin signaling pathway are found
in 90% of spontaneously arising CRCs. These mutations lead to accumulation of the β-catenin transcriptional
co-activator in the nucleus and deregulated expression of Wnt/β-catenin target genes, including Axis inhibition
two (AXIN2). The predominant role of AXIN2 has been described as a cytoplasmic protein that serves to
mitigate Wnt signaling by targeting β-catenin for proteasomal degradation. However, in CRCs, we find that
AXIN2 localizes both to cytoplasmic and nuclear compartments. We have found that AXIN2 directly represses
expression of the c-MYC proto-oncogene by forming a ternary complex with β-catenin and T-cell factor (TCF)
transcription factors at Wnt responsive DNA regulatory elements (WREs) in proximity to MYC. We therefore
hypothesize that nuclear AXIN2 regulates Wnt/β-catenin target gene expression to promote tumorigenesis. In
Aim 1, we will define the compendium of Wnt/β-catenin target genes regulated by nuclear AXIN2 and
mechanistically assess how AXIN2 regulates their expression. In Aim 2, we will evaluate whether nuclear
AXIN2 regulates the oncogenic potential of established human CRC cell lines. This work will further elucidate
how oncogenic Wnt/β-catenin signaling controls gene expression and may lead to discovery of novel genes
and pathways of potential therapeutic relevance.

## Key facts

- **NIH application ID:** 9957074
- **Project number:** 5R03CA233402-02
- **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:** 2020
- **Award amount:** $74,211
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957074

## Citation

> US National Institutes of Health, RePORTER application 9957074, Nuclear AXIN2 and Colorectal Cancer (5R03CA233402-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9957074. Licensed CC0.

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