期刊
CANCERS
卷 12, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/cancers12092342
关键词
cancer cell invasiveness; invadopodia; metastases; antagonists
类别
资金
- Ministere de la Recherche et des Technologies
- Ligue Nationale Contre le Cancer-Interregion Grand-Ouest
- Region Centre-Val de Loire (grant CancerInflam n-3)
- Association CANCEN
- University of Tours
- Charity le Cancer du sein: parlons-en!
- Region Centre-Val de Loire, a Prestige Incoming mobility fellowship (Campus France, FP7 funded research, EU)
- Fondation Tourre (France)
- Fondation pour la Recherche Medicale (FRM) [SPF201909009198]
The P2X7 receptor is an ATP-gated cation channel with a still ambiguous role in cancer progression, proposed to be either pro- or anti-cancerous, depending on the cancer or cell type in the tumour. Its role in mammary cancer progression is not yet defined. Here, we show that P2X7 receptor is functional in highly aggressive mammary cancer cells, and induces a change in cell morphology with fast F-actin reorganization and formation of filopodia, and promotes cancer cell invasiveness through both 2- and 3-dimensional extracellular matrices in vitro. Furthermore, P2X7 receptor sustains Cdc42 activity and the acquisition of a mesenchymal phenotype. In an immunocompetent mouse mammary cancer model, we reveal that the expression of P2X7 receptor in cancer cells, but not in the host mice, promotes tumour growth and metastasis development, which were reduced by treatment with specific P2X7 antagonists. Our results demonstrate that P2X7 receptor drives mammary tumour progression and represents a pertinent target for mammary cancer treatment.
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