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Updated: Jul 9, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
ATR senses stiff extracellular matrix to promote epithelial-to-mesenchymal transition and immune suppression
Xinyi Tu1,2,3, Xiangyu Zeng4, Yaoliang Sun4
1Department of Radiation Oncology.
Abstract:
Our research uncovers a role for ATR in responding to ECM stiffness and promoting epithelial-to-mesenchymal transition (EMT) and metastasis. ATR, when deubiquitinated and upregulated by USP21 under enhanced ECM stiffness conditions, phosphorylates the nuclear protein SUN2, which promotes β-catenin nuclear translocation and EMT. ATM-mediated EMT promotes polymorphonuclear myeloid-derived suppressor cell recruitment and inhibits CD103+ dendritic cells, fostering an immunosuppressive tumor milieu. ATR inhibition disrupts this malignant cascade by promoting mesenchymal-to-epithelial transition to enhance antitumor immunity and mitigate metastases. Consistently, circulating HLA-DR+ dendritic cells were also enhanced following treatment with the ATR inhibitor berzosertib in patients with therapeutically resistant early-stage breast cancer. Our data suggest that ATR-targeted therapy may be optimized by considering both DNA damage-dependent and EMT-inducing effects of ATR.
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