Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease DOI Creative Commons
Ghazaleh Khalili‐Tanha, Evette S. Radisky, Derek C. Radisky

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 11, 2025

Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells, defined by apical-basal polarity and tight intercellular junctions, acquire migratory invasive properties characteristic of mesenchymal cells. Under normal conditions, EMT directs essential morphogenetic events embryogenesis supports tissue repair. When dysregulated, contributes to pathological processes such as organ fibrosis, chronic inflammation, cancer progression metastasis. Matrix metalloproteinases (MMPs)-a family zinc-dependent proteases that degrade structural components the extracellular matrix-sit at nexus this dismantling basement membranes, activating pro-EMT signaling pathways, cleaving adhesion molecules. normally regulated, MMPs promote balanced ECM turnover support cyclical remodeling necessary for proper development, wound healing, homeostasis. abnormally drive excessive turnover, thereby promoting EMT-related pathologies, including tumor fibrotic disease. This review provides an integrated overview molecular mechanisms both initiate sustain under physiological disease conditions. It discusses how can potentiate through TGF-β Wnt/β-catenin signaling, disrupt cell-cell junction proteins, action hypoxia-inducible factors microenvironment. these pathologic remodel tissues during fuel cell invasion, metastasis, resistance therapy. Finally, explores emerging therapeutic strategies selectively target EMT, ranging from CRISPR/Cas-mediated interventions engineered inhibitors (TIMPs), demonstrates approaches may suppress without compromising its indispensable roles biology.

Язык: Английский

From Bench to Bedside: Transforming Cancer Therapy with Protease Inhibitors DOI Open Access
Alireza Shoari

Targets, Год журнала: 2025, Номер 3(1), С. 8 - 8

Опубликована: Март 3, 2025

Proteases play a pivotal role in cancer progression, facilitating processes such as extracellular matrix degradation, angiogenesis, and metastasis. Consequently, protease inhibitors have emerged promising therapeutic agents oncology. This review provides comprehensive overview of the mechanisms by which modulate biology, categorizing their target classes, including metalloproteinases, cysteine proteases, serine proteases. We discuss potential both synthetic natural inhibitors, highlighting applications preclinical clinical settings. Furthermore, challenges specificity, toxicity, resistance are addressed, alongside strategies to overcome these limitations through innovative drug designs combination therapies. The future treatment lies precision medicine, leveraging proteomic profiling tailor therapies individual tumors. underscores importance ongoing research development novel approaches harness effectively for management.

Язык: Английский

Процитировано

0
Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease DOI Creative Commons
Ghazaleh Khalili‐Tanha, Evette S. Radisky, Derek C. Radisky

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 11, 2025

Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells, defined by apical-basal polarity and tight intercellular junctions, acquire migratory invasive properties characteristic of mesenchymal cells. Under normal conditions, EMT directs essential morphogenetic events embryogenesis supports tissue repair. When dysregulated, contributes to pathological processes such as organ fibrosis, chronic inflammation, cancer progression metastasis. Matrix metalloproteinases (MMPs)-a family zinc-dependent proteases that degrade structural components the extracellular matrix-sit at nexus this dismantling basement membranes, activating pro-EMT signaling pathways, cleaving adhesion molecules. normally regulated, MMPs promote balanced ECM turnover support cyclical remodeling necessary for proper development, wound healing, homeostasis. abnormally drive excessive turnover, thereby promoting EMT-related pathologies, including tumor fibrotic disease. This review provides an integrated overview molecular mechanisms both initiate sustain under physiological disease conditions. It discusses how can potentiate through TGF-β Wnt/β-catenin signaling, disrupt cell-cell junction proteins, action hypoxia-inducible factors microenvironment. these pathologic remodel tissues during fuel cell invasion, metastasis, resistance therapy. Finally, explores emerging therapeutic strategies selectively target EMT, ranging from CRISPR/Cas-mediated interventions engineered inhibitors (TIMPs), demonstrates approaches may suppress without compromising its indispensable roles biology.

Язык: Английский

Процитировано

0