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 generate nucleotides to support cell proliferation. Here, we aim to understand a 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 cells significantly inhibits the growth, colony formation and tumor growth. Analysis of publicly available PCa RNA seq data bases revealed that PSPH overexpression and amplification is associated with alterations of metabolism and immunity. The results suggest that PSPH maybe a new target for treatment of PCa and AA CAFs may promote the proliferation of PCa.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1196239
Entities
People
- Michael Lilly
- Xiaolin Zi
Organizations
- University of California, Irvine