Mechanisms and implications of epithelial cell plasticity in the bladder

Cellular plasticity, the ability of cells to reprogramme and alter their fate, has a pivotal role in maintaining homeostasis and facilitating tissue regeneration after injury. The bladder urothelium, a dynamic transitional epithelial layer, displays a highly plastic phenotype that enables its remarkable regenerative capacity in response to wounding. During both development and repair, urothelial cells exhibit considerable plasticity through processes such as dedifferentiation, transdifferentiation and epithelial-to-mesenchymal transition. Urothelial plasticity is not only crucial for healthy tissue repair but is also involved in pathological conditions, including cancer. In bladder tumorigenesis, urothelial cells exploit plasticity to acquire new phenotypic and functional characteristics, transitioning between distinct cellular states. This plasticity contributes to tumour heterogeneity, subtype switching, progression, metastasis and resistance to therapies. These dynamic cellular transitions are regulated by intrinsic and extrinsic factors, including transcriptional and epigenetic mechanisms, as well as microenvironmental influences. Targeting urothelial plasticity could offer novel therapeutic strategies for bladder-related diseases.