ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis

• DOI: 10.1172/jci.insight.91828
• Publication Date: 2017-09-20T15:00:49Z
• Authors: Mingzhu Yin; Huanjiao Jenny Zhou; Jiqin Zhang; Caixia Lin; Hongmei Li; Xia Li; Yonghao Li; Haifeng Zhang; David G. Breckenr...; Weidong Ji; Wang Min
• Keywords: ASK1

We have recently reported that tumor-associated macrophages (TAMs) promote early transcoelomic metastasis of ovarian cancer by facilitating TAM-ovarian cell spheroid formation. ASK1 is known to be important for macrophage activation and inflammation-mediated tumorigenesis. In the present study, we show deficiency attenuates TAM-spheroid formation progression in an orthotopic model. Interestingly, stroma, but not TAMs, critical peritoneal tumor growth cancer. Moreover, overexpression inhibitory protein (suppressor cytokine signaling-1; SOCS1) vascular endothelium permeability, TAM infiltration, growth. Mechanistically, mediates degradation endothelial junction VE-cadherin via a lysosomal pathway transmigration. Importantly, pharmacological inhibitor prevents tumor-induced leakage, two mouse models. Since also associated with many other cancers, such as pancreatic colon our study provides therapeutic target treatment cancers.