Carcinoma-Associated Fibroblasts from African American Prostate Cancer Promote Aggressive Tumors: Implications for Developing Novel Therapy
Abstract
Metabolic reprogramming is one of the key characteristics of cancer and tumor microenvironment for fueling the rapid and self-sufficient growth of cancer cells. L-3- phosphoserine phosphatase (PSPH) is one of the five rate-limiting enzymes in the biosynthesis of serine from glucose, which generates nucleotides to support cell proliferation. Here, we aim to understand the role of PSPH expression and its regulation in prostate cancer (PCa) and its relation to PCa disparity. We discovered that MDAPCa2b cells, which were derived from African American (AA) PCa, and AA carcinoma-associated fibroblasts (CAFs) express much higher levels of PSPH protein compared to benign associated fibroblasts, normal prostate epithelial cells, and PCa cell lines from European American PCa. Knock-down of PSPH expression in MDAPCa2b and LNCaP cells significantly altered the expression of genes related to metabolisms (sex steroid hormone and cholesterol biosynthesis) and immunity (antigen process and presentation and interferon-related genes), which is consistent with our previous analysis of publicly available PCa RNA seq databases. The results suggest that targeting PSPH in prostate cancer can regulate tumor metabolism and immunity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1221785
Entities
People
- Huayu Wu
- Kishore Chandra
- Liankun Song
- Michael Lilly
- Vinh Le
- Xiaolin Zi
Organizations
- University of California, Irvine