The role of phosphatidylcholine metabolism in tumors.

Abstract

Phosphatidylcholine (PC), a core component of eukaryotic cell membranes essential for maintaining membrane integrity, has emerged as a critical regulator in oncogenic metabolic reprogramming. Accumulating evidence reveals that dysregulated PC metabolism constitutes a central mechanism driving malignant tumor progression. This review systematically delineates the biosynthetic pathways (Kennedy pathway, PEMT pathway, Lands cycle) and catabolic processes (phospholipase-mediated hydrolysis via PLA₂, PC-PLC, and PLD) governing PC homeostasis. We highlight how PC metabolic networks orchestrate pro-tumorigenic effects via multifaceted mechanisms, such as enhancing membrane biosynthesis to support rapid tumor proliferation, activating some proliferative signaling cascades coupled with apoptosis suppression, remodeling the immunosuppressive microenvironment, et al. Notably, small-molecule inhibitors targeting key PC metabolic enzymes (e.g., RSM-932A, FIPI) demonstrate promising anti-tumor efficacy in preclinical models, though therapeutic outcomes are constrained by metabolic plasticity and tumor heterogeneity. By integrating recent advances in lipidomics and spatial metabolomics, this synthesis not only deciphers the evolutionary logic underlying PC-driven oncogenesis but also proposes innovative therapeutic strategies combining metabolic inhibitors with immune checkpoint modulators. Our analysis provides a conceptual framework for targeting phospholipid vulnerabilities in cancer, paving the way for precision oncology applications.