# New activities of the human DEK oncogene

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $344,256

## Abstract

ABSTRACT.
This proposal builds on our past studies of the human DEK gene, which is amplified and overexpressed, and
thus implicated in many human cancer types including head and neck squamous cell carcinoma (HNSCC).
HNSCC is the sixth most common malignancy worldwide - with dismal outcomes. Identification of biomarkers
for early diagnosis and new drug targets remains imperative. DEK is a highly conserved protein that binds nucleic
acids and regulates diverse nuclear processes, including transcription. We have shown that DEK is an oncogene,
by reporting that DEK overexpression extends the life span of primary human keratinocytes, induces hyperplasia
in 3D models of epidermis, cooperates with classical oncogenes to stimulate keratinocyte transformation, and
promotes HPV+ and HPV– HNSCC and breast cancer cell proliferation and invasion. Our data also demonstrated
that DEK overexpression increases β-catenin activity, and this DEK-β-catenin axis is required and sufficient for
some cancer phenotypes.
 A major hurdle in neoplastic transformation is the ability of cells to meet high bioenergetic and biosynthetic
needs for sustained cancer cell growth. Recently, we reported that DEK overexpression increases transcription
of key enzymes in glycolysis, lactate fermentation and cholesterol synthesis, and accumulation of metabolites
that are glycolytic end products. However, it is not known whether β-catenin is required for DEK-driven metabolic
reprogramming, and we do not understand the role of glycolysis and cholesterol synthesis in DEK-driven cancer
phenotypes. Finally, in preliminary studies, we discovered that DEK is uniquely targeted to mitochondria, and
DEK overexpression stimulated cellular oxidative phosphorylation capacity. In the proposed 3 aims, we test 2
hypotheses. First, that DEK overexpression promotes HNSCC oncogenic phenotypes by 2 discrete pools of DEK
which drive metabolic deregulation, one nuclear (Aim1) and one mitochondrial (Aim2). Second, that targeting
either β-catenin, or vulnerable nodes of the metabolic signature is an effective strategy to prevent HNSCC
phenotypes. In partnership with an expert in stable isotope resolved metabolomics technologies, we will generate
an atom-resolved map of metabolic networks controlled by DEK overexpression, and will then use this map to
identify and validate novel metabolic flux vulnerabilities for drug targeting and diagnostic biomarkers (Aim3).
Taken together, the proposed experiments represent a significant first step towards innovative prevention and
treatment strategies to improve the outcomes of HNSCC via metabolic interventions.

## Key facts

- **NIH application ID:** 10740849
- **Project number:** 5R01CA239605-05
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Susanne I Wells
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $344,256
- **Award type:** 5
- **Project period:** 2019-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10740849

## Citation

> US National Institutes of Health, RePORTER application 10740849, New activities of the human DEK oncogene (5R01CA239605-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10740849. Licensed CC0.

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