Promotion of breast cancer by the DNPH1 enzyme - Research report - cellular mechanisms

Sep 23, 2026

Uploaded by Aurelia

To broaden understanding of breast cancer pathophysiology, the study investigates the understudied DNPH1 enzyme and links it to tumor aggressiveness. DNPH1 is overexpressed in breast, prostate, and lung tumors and correlates with poorer outcomes. DNPH1 downregulation or genetic ablation reduces oncogenic potential and impairs stem-cell behavior, while Dnph1 knockout suppresses HER2-mediated mammary tumor formation, angiogenesis, and elevates AMP-activated protein kinase signaling, including YAP1 phosphorylation. Results position DNPH1 as a promising cancer-therapy target.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Summary

Introduction

Results

DNPH1 overexpression in breast cancer

iScience Article Promotion of breast cancer by the DNPH1 enzyme Authors Sangphil Oh, Yuan Sui, Sook Shin, Ralf Janknecht Correspondence [ralf-janknecht@ou.edu](ralf-janknecht@ou.edu) In brief Cell biology; Cancer • The DNPH1 enzyme displays oncogenic activity in breast and lung cancer • DNPH1 can stimulate breast tumor angiogenesis • DNPH1 lowers AMP levels, thereby decreasing AMPK activity but stimulating YAP1 Oh et al., 2026, iScience 29, 115227 April 17, 2026 © 2026 The Author(s) . Published by Elsevier Inc. [https://doi.org/10.1016/j.isci.2026.115227](https://doi.org/10.1016/j.isci.2026.115227) ll iScience ll OPEN ACCESS Article Promotion of breast cancer by the DNPH1 enzyme Sangphil Oh,1,2 Yuan Sui,3 Sook Shin,1,2 and Ralf Janknecht1,2,3,4,5,* 1Department of Cell Biology, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA 2Stephenson Cancer Center, Oklahoma City, OK 73104, USA 3Department of Pathology, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA 4Department of Dermatology, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA 5Lead contact *Correspondence: [ralf-janknecht@ou.edu](ralf-janknecht@ou.edu)[ ](ralf-janknecht@ou.edu)[https://doi.org/10.1016/j.isci.2026.115227](https://doi.org/10.1016/j.isci.2026.115227) SUMMARY To broaden understanding of breast cancer pathophysiology, we investigated the highly understudied DNPH1 enzyme in this disease. We found that DNPH1 is overexpressed in breast and also in prostate and lung tumors, correlating with disease aggressiveness. DNPH1 downregulation diminished the oncogenic potential of breast cancer cells and compromised respective stem cells. Likewise, DNPH1 ablation decreased the oncogenicity of lung cancer cells. Knockout of Dnph1 in mice revealed that DNPH1 is not essential for development, yet crucial for HER2-mediated mammary tumor formation. Notably, Dnph1 knockout reduced angiogenesis in HER2-induced mammary tumors and elevated AMP levels. This was accompanied by increased AMP-activated protein kinase activity and phosphorylation of YAP1, implying tapered activity of the YAP1 oncoprotein. These data have extensively shed light onto the cellular and physiological functions of the enigmatic DNPH1 protein in cancer. Overall, this highlights that DNPH1 is a promising target for cancer therapy. INTRODUCTION Breast cancer is the second most frequently diagnosed cancer in the world. About 2.3 million persons are expected to be diagnosed with this malady in 2026, and approximately 0.67 million women will die of this disease.1 ,2 In the United States of America alone, the annual incidence of breast cancer is 0.32 million cases, and more than forty thousand patients will succumb to this malignancy.3 The numbers of diagnosed women and those perishing from breast cancer are projected to rise by 40%–50% over the next 15 years, and particularly countries with a low human development index will bear the major brunt of those increases.4 These facts underline the urgent need to improve early detection as well as to uncover new avenues of therapeutic intervention for breast cancer, which may arise through a better molecular understanding of this debilitating and often fatal disease. 2′ -Deoxynucleoside 5′ -phosphate N-hydrolase 1 (DNPH1, previously also called RCL) is a predominantly cytoplasmic enzyme that cleaves the N-glycosidic bond of selected 2′ -deoxyribonucleoside 5′ -monophosphates (dNMPs) and may be upregulated in human breast tumors.5–7 Genetic evidence suggested that high DNPH1 expression might be associated with increased breast cancer risk, yet no causal relationship has been established.8–10 Moreover, ectopic DNPH1 expression induced, albeit very inefficiently, anchorage-independent growth of Rat1A fibroblasts,11 but failed to elicit tumor formation in corresponding mouse xenograft experiments.12 These data imply that DNPH1 isnot a bona fide oncoprotein, yet co

FAQs

What does DNPH1 do in breast and other cancers, according to the study?

The study reports that DNPH1 shows oncogenic activity and is overexpressed in breast tumors as well as prostate and lung tumors, correlating with disease aggressiveness.

How does DNPH1 loss affect tumor behavior?

DNPH1 downregulation diminishes oncogenic potential in breast cancer cells and compromise related stem cells, while DNPH1 ablation decreases oncogenicity in lung cancer cells.

What signaling changes occur when DNPH1 is knocked out?

Dnph1 knockout increases AMP levels and enhances AMP-activated protein kinase activity, accompanied by increased phosphorylation of YAP1, suggesting reduced oncogenic YAP1 activity, along with reduced angiogenesis in HER2-induced mammary tumors.

Sep 23, 2026

Uploaded by Aurelia