# Defining and Characterizing Drivers of Lethal Metastatic Prostate Cancer

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $368,849

## Abstract

Prostate cancer (PC) is the second leading cause of cancer-related deaths in the USA. The goal of our 
proposed research is to identify genetic factors that are essential for the switch from indolent to lethal 
metastatic prostate cancer. We have generated primary cell lines from tumor and metastasis of the RapidCaP 
mouse model for lethal PC (PTEN and TP53 deficient). Our preliminary data highlights a fundamental shift 
in cellular phenotype and growth signaling associated with the transition to metastasis. Most importantly, the 
loss of TAM kinase receptor is key for this metastasis associated cellular reprogramming event. These 
discrete cellular states are associated with divergent signaling behavior, which enables or restricts the 
metastatic potential of cancer cells. Therefore, our focus is now on delineating the role of TAM kinases in PC 
metastasis and the signaling cascade controlling the switch from primary to distant metastatic disease in 
vivo. In this proposal we will mechanistically validate the role of TAM receptors in PC cellular lineage 
reprogramming and maintenance of pro-metastatic EMT-like phenotype (Aims 1 and 3). Next, we will assess 
the role of PI3K/mTOR signaling axis in TAM-deficient PC (Aim 2). To execute the proposed aims, we will 
closely collaborate with experts in receptor signaling and prostate cancer disease biology. Our background 
in mouse genetics, cell biology and translational oncology is well aligned with the expertise required to carry 
out the proposed work and unravel the genetic dependencies of lethal metastatic PC cells.

## Key facts

- **NIH application ID:** 10579377
- **Project number:** 5P20GM121316-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Grinu Mathew
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $368,849
- **Award type:** 5
- **Project period:** 2022-03-01 → 2023-07-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10579377

## Citation

> US National Institutes of Health, RePORTER application 10579377, Defining and Characterizing Drivers of Lethal Metastatic Prostate Cancer (5P20GM121316-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10579377. Licensed CC0.

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