Epigenetic regulation of the membrane transportome: implications for cancer progression

Cancer cells undergo extensive functional, morphological, and genetic alterations that profoundly affect proliferation, metabolism, differentiation, and communication with the surrounding microenvironment. In this context, reciprocal exchanges with the extracellular milieu play a pivotal role. These processes are mediated by membrane transport proteins collectively referred to as the "transportome", including both plasma membrane transporters and those localized to intracellular compartments that regulate trafficking between organelles. In many cancers, the transportome undergoes extensive remodeling, ranging from altered gene expression to the generation of distinct protein isoforms. These changes are driven by multiple direct and indirect epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA activity. Here, we review the rapidly expanding body of literature addressing the epigenetic regulation of the transportome in cancer, with particular emphasis on the growing number of cases in which epigenetic modulation has been demonstrated or strongly suggested. Although this field is still in its early stages, further mechanistic investigation and comprehensive characterization of these processes will be essential to fully elucidate their biological and clinical relevance. Ultimately, such advances may contribute to the development of more personalized therapeutic strategies, with the potential to improve efficacy while reducing the side effects associated with conventional treatments.