CPS1 promotes colorectal cancer progression by inducing EMT and activating TGF-β/Smad signaling pathway
TL;DR
These findings identify CPS1 as a potential prognostic biomarker and therapeutic target in CRC and suggest that CPS1 may contribute to the malignant progression and metastasis of CRC, potentially through involvement in the epithelial-mesenchymal transition (EMT) process and TGF-β signaling pathway.
Abstract
Summary Colorectal cancer (CRC) is a highly lethal digestive malignancy, particularly in metastatic cases. Carbamoyl-phosphate synthase 1 (CPS1), a key mitochondrial enzyme involved in the urea cycle, has been implicated in multiple cancers. However, its role in CRC remains poorly understood. This study demonstrated that CPS1 expression was significantly upregulated in CRC tissues and was associated with aggressive clinicopathological characteristics and poor prognosis. Functional experiments revealed that CPS1 knockdown markedly suppressed CRC cell proliferation, migration, invasion, and tumorigenicity, whereas CPS1 overexpression exerted opposite effects. Mechanistically, CPS1 downregulation increased E-cadherin expression and decreased the expression of ZEB1, slug, N-cadherin, vimentin, MMP2, and p-SMAD2/3, while CPS1 overexpression reversed these changes, suggesting that CPS1 may contribute to the malignant progression and metastasis of CRC, potentially through involvement in the epithelial-mesenchymal transition (EMT) process and TGF-β signaling pathway. Collectively, our findings identify CPS1 as a potential prognostic biomarker and therapeutic target in CRC.