Year: 2026
Type: article
Abstract: E-cadherin suppresses invasion and promotes metastasis in invasive ductal breast cancer, through suppression of reactive oxygen species (ROS). We sought to determine the cellular source of apoptosis-inducing ROS and to identify the domains of E-cadherin that are essential for cancer cell survival. Inhibition of mitochondria-derived ROS was sufficient to rescue cell death following E-cadherin deletion, in both 3D colony formation and in vivo metastasis assays. We next generated Cdh1 constructs by mutating amino acids or deleting domains, then tested their ability to rescue colony formation in E-cadherin-deleted cells. Surprisingly, E-cadherin constructs in which the extracellular domains were deleted, adhesion was compromised, or catenin interactions were blocked could rescue elevated mitochondrial ROS and 3D colony formation. Conversely, a construct lacking the cytoplasmic domain was unable to rescue ROS or cell death. Our findings reveal that E-cadherin's ability to regulate mitochondrial ROS, cancer cell survival, and metastatic outgrowth is separable from its role in intercellular adhesion.
Source: The Journal of Cell Biology
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: American Heart Association, Breast Cancer Research Foundation, Barth Syndrome Foundation, Jayne Koskinas Ted Giovanis Foundation for Health and Policy, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences
Awards: G2043406584, G2990623361, G3343988890, Role of cardiolipin in cardiac ADP/ATP translocator activity, Cellular Signaling in Drug Induced Toxicity, Molecular basis to regulate the cardiac-specific form of mitochondrial phospholipid cardiolipin, Center for 3D Imaging in Cancer Cell Biology, Mapping the single cell state basis of metastasis in space and time, Decoding dynamic interplay between signaling and membranes in chemotaxis by molecular actuators, Medical Scientist Training Program, Regional Oncology Research Center, Endoplasmic reticulum-assisted mitochondrial precursor biogenesis and quality control, An intimate and multifaceted partnership: cardiolipin and the mitochondrial ADP/ATP carrier
OpenAlex ID: W7204811399