Identification of a new molecular target: CD95 promotes breast metastasis by activating NHE1
ABSTRACT: Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to cancer cell dissemination in patients affected by triple negative breast cancer (TNBC). The motility signaling pathway elicited by cl-CD95L remains poorly defined.
A collaboration with Dr L. Counillon Team highlights that in the presence of cl-CD95L, CD95 activates the PI3K and RhoA signaling pathways, which together orchestrate activation of the Na+/H+ exchanger NHE1. Inhibition of NHE1 in TNBC cells exposed to cl-CD95L blocks the cell migration. Together, these original findings demonstrate that inhibition of NHE1 using therapeutics such as amiloride or cariporide may turn out to be an attractive approach to prevent metastasis in breast cancer patients.
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