# Mechanism of cancer progression in prostate cancer cells

> **NIH NIH P20** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2021 · $222,000

## Abstract

Summary of molecular mechanism of prostate cancer progression
Prostate cancer is the most common cancer of men in the world. Age, ethnicity, diet, gene
mutations and a number of other factors are associated with increased risk for prostate cancer.
However, the cellular progression of a prostate tumor cell are not well known. Diepoxybutane
(DEB) is a carcinogenic metabolite of 1,3-butadiene (BD), a hazardous chemical used in rubber
production and present in automobile exhaust and tobacco smoke. Efforts to understand
mechanisms of BD toxicity have recently demonstrated that DEB causes the cell cycle to stop
and further induces apoptosis upon binding to DNA. However, we have found that at low
concentrations (0.5 µM), DEB resulted in DU145 cell migration and activates PI3K, EMT marker
E-Cadherin and the Cancer Stem Cell (CSC) markers SSEA-4 and Oct3/4 in 2D cultures of
DU145 prostate cancer cells but its role is unclear under 3D cell culture conditions. We
hypothesize that DEB may be effective in inducing Epithelial-to-Mesenchymal Transition (EMT)
and stimulates drug resistant mechanisms through the activation of specific cell signaling
pathways. We will test our hypothesis by two Aims. We will first to identify the functional role of
the PI3K/AKT/ mTOR cell signaling pathway in prostate cancer progression by the use of
commercially available signal transduction inhibitors. We then will investigate the new molecular
mechanism by which DEB promotes prostate cancer progression due to network of signaling
pathways. This Aim will be conducted single-cell transcriptome (scRNAseq) and proteomic
analyses (Cell signal and Apoptotic antibody arrays) on control versus DEB-treated spheroids to
identify the genes/ proteins that show altered expression in prostate cancer cells exposed to
DEB. Functional studies will be conducted by performing CRISPR/Cas9 knockdown or RNAi of
new key gene or genes with known association with cell migration and/or acquisition of drug
resistance.
The results obtained from this project will help us to understand the role of DEB on prostate
cancer progression and will provide an insight on anticancer drug metabolism that leads to
chemotherapy resistance. Furthermore, the results obtained from this project will provide
insights into new important approaches to combat prostate cancer which may also be applicable
to other types of cancer. More importantly, the knowledge acquired at the conclusion of this
project may enhance our ability to fight cancer progression.

## Key facts

- **NIH application ID:** 10104819
- **Project number:** 1P20GM135000-01A1
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** xiaoping Yi
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $222,000
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104819

## Citation

> US National Institutes of Health, RePORTER application 10104819, Mechanism of cancer progression in prostate cancer cells (1P20GM135000-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10104819. Licensed CC0.

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