# Nuclear Neuropilin2: a novel molecular mediator for aggressive Prostate Cancer

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $340,803

## Abstract

Abstract
Localized prostate cancer is often categorized as either indolent or aggressive based largely on
clinical and pathological features. Despite our understanding of genetic alterations that are
associated with different stages of prostate cancer (PCa), there is no clear molecular classification
system, which can predict the risk for developing aggressive PCa. As a result, it is currently
difficult to discriminate the aggressive and indolent PCa in their early stages, and develop
appropriate therapy for the patients with aggressive cancer. Surgery, radiation and less often
androgen deprivation therapies are the available treatment options for localized tumor, although
cancers of 30-35% of patients recur and some of them evolve into metastatic disease. There are
very limited treatment options for advanced stage PCa. It is therefore important to identify the
molecular mediators that promote the advancement of PCa. A comprehensive knowledge on the
function of these mediators will not only help us to determine the molecular factors that can
distinguish the aggressive and indolent PCa but also to establish effective treatment modalities
for those patients who are at high risk to develop metastatic cancer. Our preliminary results
indicated that Neuropilin-2 (NRP2) could be a mediator of aggressive PCa by regulating the global
transcription of genes required for cancer promotion. Mechanistically, NRP2 can translocate from
ER to nuclear membrane through retrograde transport and stabilize the transcription machineries
necessary for the expression of cancer promoting genes. Based on these novel observations, we
hypothesized that nuclear NRP2 is critical for the transcription of genes required for the
advancement of PCa. Hence, NRP2 is not only a predictor for aggressive PCa but also a target
for effective treatment strategy. Two specific aims have been proposed. In aim 1, we will study
the underlying mechanisms of how nuclear membrane-bound NRP2 interacts with the
transcription factors in PCa cells and facilitates their activity. We will also determine using a cohort
of human PCa tissues whether nuclear NRP2 can be a prognostic factor, which can discriminate
between indolent and aggressive PCa. Aim 2 will focus on the molecular mechanism of how
NRP2 migrates to nuclear membrane and determine whether inhibition of this translocation can
block the prostate tumor growth. Altogether, our proposal will determine how nuclear NRP2
promotes PCa and thus can be an effective predictor for aggressive PCa. Moreover, it will identify
whether targeting NRP2 axis such as blocking its nuclear transport is an effective therapeutic
approach to treat aggressive PCa.

## Key facts

- **NIH application ID:** 10375361
- **Project number:** 5R01CA239343-03
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Kaustubh Datta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $340,803
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375361

## Citation

> US National Institutes of Health, RePORTER application 10375361, Nuclear Neuropilin2: a novel molecular mediator for aggressive Prostate Cancer (5R01CA239343-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375361. Licensed CC0.

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