Convergence of epithelial-mesenchymal transition and mitochondrial dynamics: Mechanisms and therapeutic opportunities in cancer metastasis

Epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells acquire mesenchymal characteristics, including enhanced motility. While EMT plays essential roles in embryonic development and tissue repair, its dysregulation is closely associated with cancer metastasis and fibrotic diseases. The active and context-dependent energy demands of EMT highlight the importance of mitochondrial function and dynamics, particularly mitochondrial fusion and fission, in facilitating EMT. Recent findings reveal a critical yet underexplored role of mitochondrial dynamics, especially fusion and fission, in supporting EMT and cancer metastasis through metabolic reprogramming and redox signaling. Dysregulation of mitochondrial dynamics has been implicated in EMT-related diseases, especially cancer and fibrosis, both of which share common pathological features such as chronic inflammation, extracellular matrix remodeling, and sustained EMT activation. Despite growing interest, the intersection of mitochondrial dynamics, stress responses, and EMT remains insufficiently studied, particularly in the context of progressive diseases such as cancer. This review addresses this gap by exploring the interplay between mitochondrial dynamics and EMT in cancer metastasis, highlighting potential vulnerabilities and therapeutic opportunities. Understanding the convergence of EMT and mitochondrial dynamics offers a novel perspective on cancer progression and paves the way for targeted interventions. Moreover, the study of mitochondrial dynamics in fibrosis may provide insights for therapeutic strategies against cancer metastasis.