Mechanisms of cellular fitness and cell competition: Towards an integrated view.

Abstract

Cell competition is a fundamental mechanism of tissue quality control that enables the selective elimination of less fit, mis-specified, diseased or aged cells. By shaping tissue composition, it plays a critical role in development, organismal health and a wide range of physiological and pathological contexts, including cancer. As its biological significance continues to grow, elucidating the molecular mechanisms underlying cell competition is essential for advancing our understanding of tissue biology, disease progression and future therapeutic strategies. In this review, we highlight recently identified, evolutionarily conserved pathways that govern cell competition through metabolites and systemic signals, proteostasis and mechanical exchange. By integrating findings across species and pathways, we reveal how these distinct mechanisms may intersect and coordinate to determine competitive outcomes, providing a conceptual framework to inform and guide future research.