The cleaved FAS ligand activates the Na+/H+ exchanger NHE1 through Akt/ROCK1 to stimulate cell motility

Michaël Monet (1) , Mallorie Poet (1) , Sébastien Tauzin (2) , Amelie Fouque (3) , Auréa Cophignon (1) , Dominique Lagadic-Gossmann (2) , Pierre Vacher (4) , Patrick Legembre (3, 1) , Laurent Counillon (1)

1 LP2M - Laboratoire de PhysioMédecine Moléculaire
2 Irset - Institut de recherche en santé, environnement et travail
3 OSS - Oncogenesis Stress Signaling
4 CRCTB - Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux]

Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na+/H+ exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration. Confirming these pharmacologic data, disruption of the Akt and ROCK1 phosphorylation sites on NHE1 decreases cell migration in cells exposed to cl-CD95L. Together, these findings demonstrate that NHE1 is a novel molecular actor in the CD95 signaling pathway that drives the cl-CD95L-induced cell migration through both the Akt and RhoA signaling pathways.

Keywords: Cell migration; Metastasis; Cell migration

Domains: Life Sciences [q-bio]; Cancer; Life Sciences [q-bio]; Cellular Biology

Michaël Monet, Mallorie Poet, Sébastien Tauzin, Amelie Fouque, Auréa Cophignon, et al.. The cleaved FAS ligand activates the Na+/H+ exchanger NHE1 through Akt/ROCK1 to stimulate cell motility. Scientific Reports, 2016, 6 (1), pp.28008. ⟨10.1038/srep28008⟩. ⟨hal-01334067⟩