Back to Search
Start Over
CD95L cell surface cleavage triggers a prometastatic signaling pathway in triple-negative breast cancer.
- Source :
-
Cancer research [Cancer Res] 2013 Nov 15; Vol. 73 (22), pp. 6711-21. Date of Electronic Publication: 2013 Sep 26. - Publication Year :
- 2013
-
Abstract
- Triple-negative breast cancers (TNBC) lacking estrogen and progesterone receptors and HER2 amplification have a relatively high risk of metastatic dissemination, but the mechanistic basis for this risk is not understood. Here, we report that serum levels of CD95 ligand (CD95L) are higher in patients with TNBC than in other patients with breast cancer. Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors generates a gradient that promotes cell motility due to the formation of an unconventional CD95-containing receptosome called the motility-inducing signaling complex. The formation of this complex was instrumental for Nox3-driven reactive oxygen species generation. Mechanistic investigations revealed a Yes-Orai1-EGFR-PI3K pathway that triggered migration of TNBC cells exposed to CD95L. Our findings establish a prometastatic function for metalloprotease-cleaved CD95L in TNBCs, revisiting its role in carcinogenesis.<br /> (©2013 AACR)
- Subjects :
- Adenocarcinoma metabolism
Animals
Antigens, Surface metabolism
Cell Movement
Female
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Neoplasm Metastasis
Proteolysis
Reactive Oxygen Species metabolism
Signal Transduction physiology
Triple Negative Breast Neoplasms metabolism
Tumor Cells, Cultured
Adenocarcinoma pathology
Fas Ligand Protein metabolism
Triple Negative Breast Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 73
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 24072745
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-13-1794