# Role of the DNPH1 Enzyme in Breast Cancer

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $357,206

## Abstract

Breast cancer is amongst the most prevalent causes of death in the US. As such, despite great
progress in our understanding of this disease, there still remains a dire need to explore the molecular
mechanisms involved in breast tumorigenesis that will ultimately lead to new treatments and improved
clinical outcomes. DNPH1 is a 2'-deoxynucleoside 5'-monophosphate N-hydrolase, whose enzymatic
activity might affect nucleotide metabolism and increase levels of 2-deoxyribose that may act as an
angiogenic factor. However, the precise physiological functions of DNPH1 and its mechanisms of
action have remained unresolved. Notably, our published and new preliminary data demonstrate that
DNPH1 is especially overexpressed in aggressive breast tumors, yet no proof of a causal relationship
between DNPH1 and breast cancer formation has been established.
 Here, we provide in vivo evidence that DNPH1 is a promoter of tumor development: its ablation in
mice impairs mammary tumor formation, angiogenesis and metastasis induced by the HER2
oncogene. Based on these and further preliminary data, we posit that DNPH1 promotes breast
tumorigenesis and, accordingly, is a valid novel drug target. Specifically, we hypothesize that DNPH1
induces tumor angiogenesis and stimulates the oncogenic potential of breast cells by modulating the
AMPK and Hippo/YAP1 signaling pathways. To test these hypotheses, we propose three specific
aims: (i) To elucidate how DNPH1 affects cell physiology. (ii) To determine how DNPH1 stimulates
angiogenesis. (iii) To decipher how DNPH1 modulates cancer cell signaling.
 Completion of these studies will greatly advance our mechanistic understanding of DNPH1 and
its role in breast tumor development. Furthermore, our research is expected to highlight DNPH1 as a
promising new drug target for breast cancer. Of note, because DNPH1 is an enzyme, small molecule
drugs can be designed to inhibit its catalytic activity. Lastly, since our DNPH1 knockout mice are
viable and present no obvious pathological phenotype, DNPH1 inhibitors are predicted to selectively
affect cancer cells and thus display minimal side effects, a highly desirable scenario for any
therapeutic drug.

## Key facts

- **NIH application ID:** 9848517
- **Project number:** 5R01CA233613-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** RALF JANKNECHT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,206
- **Award type:** 5
- **Project period:** 2019-01-09 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9848517

## Citation

> US National Institutes of Health, RePORTER application 9848517, Role of the DNPH1 Enzyme in Breast Cancer (5R01CA233613-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9848517. Licensed CC0.

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