Deciphering the Functional Mechanisms of eIF3f in Tumors and Exploring Targeted Therapies

ABSTRACT Eukaryotic translation initiation factor 3 subunit F (eIF3f) is a critical component of the eIF3 complex and plays a pivotal role in diverse biological processes, including cell proliferation, apoptosis, adhesion, and transcriptional regulation. Recent studies have revealed that eIF3f is aberrantly expressed in multiple malignancies and exhibits a striking context‐dependent functional profile. In solid tumors such as hepatocellular carcinoma (HCC), colorectal cancer (CRC), and prostate cancer (PCa), elevated eIF3f expression correlates with poor patient prognosis, indicating an oncogenic role. Conversely, in pancreatic cancer (PC) and melanoma (MM), reduced or absent eIF3f expression promotes tumor progression, suggesting a tumor‐suppressive function. This functional plasticity indicates that eIF3f is not a simple oncogenic driver but rather a molecular hub that integrates diverse cellular signals. This review systematically delineates the structural characteristics and biological functions of eIF3f, summarizing its expression patterns and underlying molecular mechanisms across various malignancies. Building on this, we propose an integrated mechanistic framework that attributes the functional plasticity of eIF3f to differential upstream signaling networks, heterogeneity in post‐translational modification profiles, and the remodeling status of the tumor microenvironment (TME). Furthermore, we critically evaluate the strength of evidence supporting eIF3f as a diagnostic and prognostic biomarker, identify methodological bottlenecks and translational challenges in current targeting strategies, and outline priority research directions, including elucidating the structural biological basis of its functional plasticity and developing context‐specific intervention strategies. By integrating mechanistic insights with clinical relevance, this review aims to establish a conceptually coherent and mechanistically testable theoretical framework for eIF3f research, guiding the design of precision stratified therapeutic approaches and facilitating its substantive translation from basic research to clinical application.