# Defining the role of NUDT5 in ovarian cancer

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $45,643

## Abstract

Ovarian cancer patients are burdened with a lack of effective therapeutic options resulting in a low survival rate
due to chemotherapy resistance, recurrence, and metastasis. The overall goal of the proposed project is to
establish innovative anti-cancer drug targets by mapping mechanical regulators of ovarian cancer progression.
Cancer metastasis requires cells to deform and migrate through confined spaces. To survive, cancer cells must
sense physical forces and adapt to maintain cellular and nuclear mechanical homeostasis. If we could map the
mechanical regulators of cancer cells—molecules that control cell deformability and migration—this would
enable us to define novel, complementary treatment strategies. To identify novel mechanical regulators, we
developed a high throughput deformability screen that tested the effects of 1280 compounds (Library of
Pharmacologically Active Compounds) on the deformability of human high-grade serous ovarian cancer
(OVCAR5) cells. Our screen revealed drug compounds that reduced cell deformability. A meta-analysis across
top drug hits revealed NUDT5 as a predicted regulator of cellular mechanical behaviors. NUDT5 is a member of
the Nudix (nucleoside diphosphate linked moiety X) hydrolase superfamily. Our preliminary analyses revealed
NUDT5 is highly expressed in various cancer types compared to normal tissue. My preliminary data shows that
NUDT5 regulates cell stiffness, morphology, and migration in OVCAR5 cells.
The goal of my project is to test
the hypothesis that NUDT5 drives ovarian cancer progression by regulating cancer cell mechanical behaviors.
In Aim 1, I will assess how NUDT5 relates to ovarian cancer progression by measuring NUDT5 expression and
localization at different disease stages in distinct histological subtypes, including high-grade serous (HGSOC)
and clear cell (OCCC) carcinoma tumors using patient tissue microarrays. I will also examine in vitro how NUDT5
regulates PARP inhibitor resistance and ovarian cancer cell behaviors, such as proliferation, migration, spheroid
formation, and invasion. In Aim 2, I will determine the role of NUDT5 activity in catalyzing ATP production for
actin cytoskeletal and nuclear remodeling following confined migration. Understanding how NUDT5 regulates
cancer cell mechanical behaviors will guide future clinical treatment strategies to improve patient survival.

## Key facts

- **NIH application ID:** 10998986
- **Project number:** 1F31CA288105-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Angelina Marybelle Flores
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $45,643
- **Award type:** 1
- **Project period:** 2024-08-16 → 2027-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998986

## Citation

> US National Institutes of Health, RePORTER application 10998986, Defining the role of NUDT5 in ovarian cancer (1F31CA288105-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10998986. Licensed CC0.

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