PABPC1 in Cancer: From a Translational Housekeeper to a Stress-Responsive Regulatory Hub

PABPC1, long recognized as a constitutive translational housekeeper, has emerged as a stress-responsive translational reprogramming hub in cancer. This review synthesizes recent paradigm shifts that redefine PABPC1 function: From global translation maintenance to selective oncogenic mRNA amplification via liquid-liquid phase separation; from binary protein-RNA interactions to complex regulatory networks involving lncRNAs and circRNAs that modulate PABPC1 stability, localization, and target selectivity; and from diffuse cytoplasmic distribution to functionally compartmentalized condensates. PABPC1 integrates diverse post-translational modifications, including SUMOylation, acetylation, and ubiquitination, that enable stress adaptation, and actively regulates alternative polyadenylation to influence 3'UTR length and gene expression. Positioned at the convergence point of multiple oncogenic signaling pathways (PI3K/AKT, Wnt/β-catenin, NF-κB, and etc.), PABPC1 converts upstream signals into translational outputs that drive tumor progression, metastasis, and therapy resistance across malignancies. Its functional duality, context-dependent activities, and paralog-specific roles underscore both the complexity and therapeutic potential of targeting this multifaceted RNA-binding protein.