# Sex specific epigenetic regulation of colon cancer metastasis

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $403,649

## Abstract

Colorectal cancer (CRC) is the third leading cause of cancer death in US and is characterized by signature
mutations of APC, p53, KRAS, SMAD4, among other genetic alterations. It is well established that male CRC
patients have worse prognosis than that of female patients, but the underlying mechanism is largely undefined.
Recent efforts in large scale whole genome and whole exome sequencing of metastatic CRC samples have not
identified novel metastatic promoting genes suggesting metastatic progression may be largely regulated by
epigenetic mechanisms. We have recently established an inducible oncogenic KRas metastatic CRC animal
model and employing this model we have identified a male specific Y-chromosome residing gene- KDM5D, as
a key regulator of CRC metastatic progression. This discovery is exciting as it connects sex biased CRC
progression with an epigenetic regulator that is druggble. In this proposal, we will employ both in vitro and animal
models to elucidate the function of KDM5D in CRC progression and define novel therapeutic approach targeting
CRC metastasis. To achieve this goal, we propose the following specific aims. 1. Elucidate the role of KDM5D
in CRC progression; 2. Define Kras mediated KDM5D upregulation in CRC and KDM5D downstream targets in
promoting metastasis; 3. Mechanistic understanding of KDM5D promotion of metastasis in vivo.

## Key facts

- **NIH application ID:** 10443932
- **Project number:** 1R01CA262798-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Y. Alan Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $403,649
- **Award type:** 1
- **Project period:** 2022-09-06 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443932

## Citation

> US National Institutes of Health, RePORTER application 10443932, Sex specific epigenetic regulation of colon cancer metastasis (1R01CA262798-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10443932. Licensed CC0.

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