Permeable Lung Vasculature Creates Chemoresistant Endothelial Niche by Producing SERPINE1 at Breast Cancer Metastatic Sites.

ABSTRACT: Chemotherapy resistance remains a major obstacle for eradicating metastatic cancer cells in distant organs. We identified that endothelial cells (ECs) in the lungs, where breast cancer cells often metastasize, form a chemoresistant perivascular niche for disseminated breast cancer cells. By investigating the lung EC secretome activated by metastasis, we found that serine protease inhibitor family E member 1 (SERPINE1), encoded by Serpine1, is upregulated in metastasis-associated lung ECs. This upregulation shields cancer cells from paclitaxel-induced apoptosis and promotes cancer stem cell properties. Serpine1 expression appears to be driven by YAP-TEAD activation in lung ECs that lose cell-cell contact, a phenomenon associated with increased vascular permeability in lungs affected by meta

SUBMITTER: Hongu T 

PROVIDER: S-EPMC12127090 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature