Proline synthetase PYCR1 acts as a metabolic reprogrammer dictating breast cancer stemness under chronic stress

Aberrant proline metabolism contributes to cancer progression, yet the underlying mechanism of proline metabolic disorders in regulating cancer stem-like cells (CSCs) remains unclear. Here, we find that proline synthetase PYCR1 is critical for breast cancer stemness and tumor growth through synthesizing proline. To explore the downstream targets responsible for the increase in proline-mediated stem-like traits in breast cancer, we performed RNA-seq based transcriptome analysis of PYCR1-knockdown (shP1-1 and shP1-2) MDA-MB-231 cells versus control (shNC) MDA-MB-231 cells. Among the differentially expressed genes (DEGs) identified in shP1-1 and shP1-2 cells, 361 genes and 214 genes were downregulated, respectively. We then performed KEGG pathways enrichment analysis in downregulated genes and found that the cGMP-PKG signaling pathway was among the top 1 enriched pathways in both shP1-1 and shP1-2 groups. RNA-seq data of the MDB-MA-231 cells in Ctrl, shP1, shP2 group.