# Unraveling KLF4 dependency in metastatic osteosarcoma

> **NIH NIH F31** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $46,036

## Abstract

PROJECT SUMMARY
While metastasis is the cause of >90% of cancer patient deaths, the majority of targeted therapies are developed
based on the biology of the primary tumor. This discrepancy highlights the pressing clinical need to better
understand what gives cancers the ability to colonize and thrive within a new microenvironment. For
osteosarcoma (OS), there are no targeted anti-metastatic therapies, despite nearly all patients presenting with
some degree of metastatic burden. Recent studies from our laboratory have demonstrated the process of OS
lung metastasis is driven by alterations in the enhancer landscape. Metastasis-specific variant enhancer loci
(met-VELs) are ubiquitous, and regulate genes critical for growth of this primary bone cancer within the lung.
However, the heterogeneity of OS has limited the clinical translation of these findings. A unifying molecular
mechanism upstream of the enhancer remodeling associated with metastasis will therefore provide novel nodes
for therapeutic targeting. Combining comprehensive enhancer analysis with in vivo functional genomic
screening, I have identified the pluripotency factor KLF4 as enriched at met-VELs and critical for lung metastasis.
The goals of this proposal are to determine if KLF4 is necessary and sufficient for OS metastasis through its role
in maintaining and generating stem cell-like enhancer chromatin. Successful completion of this study will not
only reveal new therapeutic targets and prognostic biomarkers, but may also inform the treatment of patients
suffering from other metastatic cancers.

## Key facts

- **NIH application ID:** 10101479
- **Project number:** 5F31CA247266-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** William Dean Pontius
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101479

## Citation

> US National Institutes of Health, RePORTER application 10101479, Unraveling KLF4 dependency in metastatic osteosarcoma (5F31CA247266-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10101479. Licensed CC0.

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