Epithelial-Mesenchymal Plasticity in Endocrine Health and Disease: Hormonal Regulation, Cellular Crosstalk, and Therapeutic Opportunities

Epithelial-mesenchymal plasticity (EMP) refers to the ability of epithelial cells to dynamically transition across a spectrum of phenotypic states through epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and intermediate or hybrid epithelial/mesenchymal (E/M) states. Rather than representing a binary switch, EMP is now recognized as a highly dynamic and context-dependent process that contributes to tissue development, homeostasis, repair, regeneration, fibrosis, and disease progression. These phenotypic transitions influence fundamental cellular properties, including polarity, adhesion, migration, stemness, differentiation, metabolism, immune interactions, and resistance to cellular stress.The endocrine system represents an important yet still incompletely explored regulator of epithelial plasticity. Steroid and peptide hormones, endocrine and paracrine mediators, growth-factor networks, and their downstream signaling pathways can profoundly influence EMT, MET, and hybrid E/M states. Conversely, changes in cellular plasticity may alter hormone responsiveness, receptor expression, endocrine signaling networks, and communication between epithelial cells and surrounding stromal, immune, vascular, and progenitor cell populations. EMP should therefore be considered not only as a downstream response to hormonal cues, but also as an integral component of the cellular networks governing endocrine tissue function and adaptation.This bidirectional relationship is particularly relevant in endocrine and hormone-responsive tissues, where dysregulated cellular plasticity may contribute to tumor initiation and progression, metastatic dissemination, fibrosis, metabolic dysfunction, altered tissue remodeling, and impaired regeneration. Endocrine-related cancers provide prominent examples, but similar mechanisms are increasingly being recognized in non-neoplastic endocrine and metabolic conditions. Furthermore, advances in single-cell and spatial omics, organoids, advanced cellular models, systems biology, and computational approaches are revealing previously unrecognized cellular states and signaling interactions involved in endocrine regulation of EMP. A broader understanding of the mechanisms connecting endocrine signaling, cellular plasticity, and intercellular communication may therefore provide new insights into tissue homeostasis and disease while identifying biomarkers, molecular vulnerabilities, and potential therapeutic targets.This Research Topic aims to provide an updated and multidisciplinary perspective on epithelial-mesenchymal plasticity in endocrine health and disease, with particular emphasis on the molecular and cellular mechanisms through which hormonal and endocrine signals regulate epithelial cell states and on how these transitions, in turn, influence endocrine function and cellular communication. Building upon the established concepts of EMT and MET, the Research Topic will place particular emphasis on the dynamic nature of EMP, including partial EMT, hybrid epithelial/mesenchymal states, phenotypic reversibility, and cellular heterogeneity. We aim to bring together studies addressing endocrine regulation of cellular plasticity across physiological and pathological contexts, ranging from tissue homeostasis and regeneration to fibrosis, metabolic dysfunction, and endocrine-related malignancies. Particular attention will be given to the interaction between epithelial plasticity and the tissue microenvironment, including immune, stromal, vascular, and stem/progenitor cell compartments, as well as to the signaling and metabolic networks that determine cellular state transitions. Studies employing advanced experimental and computational approaches to characterize EMP and its endocrine regulation are particularly encouraged. Ultimately, this Research Topic seeks to bridge fundamental cellular endocrinology with disease mechanisms and therapeutic discovery, providing a platform for identifying molecular determinants of epithelial plasticity that may serve as biomarkers or targets for future therapeutic intervention. Contributions should demonstrate a clear connection with endocrine or hormonal regulation and provide mechanistic insight at the cellular and/or molecular level. Studies focusing exclusively on descriptive clinical associations or on EMT/EMP without a defined endocrine component fall outside the intended scope of the Research Topic. This Research Topic welcomes Original Research, Reviews, Mini Reviews, Perspectives, Methods, and other relevant article types addressing, but not limited to, the following areas:• Hormonal and endocrine regulation of epithelial-mesenchymal plasticity. Molecular mechanisms through which steroid hormones, peptide hormones, endocrine mediators, hormone receptors, and associated signaling networks regulate EMT, MET, partial EMT, and hybrid epithelial/mesenchymal states.• Epithelial-mesenchymal plasticity in endocrine and hormone-responsive tissues. Physiological and pathological roles of EMP in tissues such as the pituitary, thyroid, adrenal gland, pancreas, reproductive system, breast, prostate, liver, and other endocrine or hormonally regulated tissues.• EMP in endocrine-related cancers and tumor progression. Interactions between hormonal signaling and epithelial plasticity in tumor initiation, invasion, metastasis, stemness, therapeutic resistance, dormancy, and disease recurrence, including mechanisms governing transitions between epithelial, mesenchymal, and hybrid phenotypes.• Cellular crosstalk and the endocrine tissue microenvironment. Interactions among epithelial cells, immune cells, fibroblasts, endothelial cells, stem/progenitor cells, and other components of the tissue microenvironment, with particular emphasis on how endocrine, paracrine, and juxtacrine signals modulate cellular plasticity.• Epithelial plasticity in tissue homeostasis, remodeling, fibrosis, and regeneration. Roles of EMT, MET, and intermediate cellular states in physiological tissue turnover, wound healing, regenerative responses, fibrotic remodeling, and restoration or loss of endocrine tissue function.• Signaling, metabolic, and epigenetic control of endocrine-associated EMP. Intracellular signaling pathways, transcriptional and epigenetic programs, non-coding RNAs, metabolic reprogramming, oxidative stress, mechanotransduction, and extracellular cues that integrate endocrine signals with epithelial cell-state transitions.• Cellular heterogeneity and emerging models for studying EMP. Application of single-cell and spatial omics, organoids, 3D culture systems, co-culture models, microphysiological systems, lineage tracing, live-cell approaches, and other advanced methodologies for dissecting endocrine-regulated cellular plasticity.• Biomarkers, predictive models, and therapeutic targeting of epithelial plasticity. Identification of biomarkers and molecular signatures of EMP; systems biology and computational modeling of endocrine-regulated cellular states; and strategies aimed at modulating plasticity, hormonal signaling, or their downstream pathways for therapeutic purposes. Topic editors: Angelo Canciello, Beatrice Dufrusine Source: https://www.frontiersin.org/research-topics/86274/epithelial-mesenchymal-plasticity-in-endocrine-health-and-disease-hormonal-regulation-cellular-crosstalk-and-therapeutic-opportunities