WASH activation controls endosomal recycling and EGFR and Hippo signaling during tumor-suppressive cell competition.

ABSTRACT: Cell competition is a conserved homeostatic mechanism whereby epithelial cells eliminate neighbors with lower fitness. Cell communication at the interface of wild-type "winner" cells and polarity-deficient (scrib^-/-) "losers" is established through Sas-mediated Ptp10D activation in polarity-deficient cells. This tumor-suppressive cell competition restrains EGFR and Hippo signaling and enables Eiger-JNK mediated apoptosis in scrib^-/- clones. Here, we show that the activation state of the endosomal actin regulator WASH is a central node linking EGFR and Hippo signaling activation. The tyrosine kinase Btk29A and its substrate WASH are required downstream of Ptp10D for "loser" cell elimination. Constitutively active, phosphomimetic WASH is sufficient to induce both EGFR a

SUBMITTER: Liu D 

PROVIDER: S-EPMC9587002 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature