期刊
CANCER SCIENCE
卷 113, 期 7, 页码 2457-2471出版社
WILEY
DOI: 10.1111/cas.15375
关键词
angiogenesis; cell adhesion; CTGF; extracellular ATP; integrin beta 1
类别
资金
- National Natural Science Foundation of China [81872382, 81672790, 81621063]
Extracellular ATP promotes the migration, angiogenesis, adhesion, and transmigration ability of TNBC cells and endothelial cells through upregulation of CTGF, thereby stimulating TNBC metastasis. Extracellular ATP or CTGF could be an effective target for TNBC therapy.
Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple-negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2-YAP-CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin beta 1 on TNBC cells and VCAM-1 on ECs. Both apyrase (ATP-diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy.
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