PXD061223

PXD061223 is an original dataset announced via ProteomeXchange.

Title	E-cadherin mechanotransduction activates EGFR/ERK signaling by inducing ligand shedding
Description	The behavior of cells is governed by signals originating from their local environment, including mechanical forces that cells experience. Forces are transduced by mechanosensitive proteins, which can impinge on signaling cascades that are also activated by growth factor receptors upon ligand binding. However, the interplay between these mechanical and biochemical signals in the regulation of intracellular signaling networks remains incompletely understood. To elucidate this mechanochemical crosstalk, we conducted phosphoproteomic and transcriptomic analyses on epithelial monolayers subjected to mechanical strain. This approach revealed ERK signaling as a predominant strain-activated hub, initiated at the level of the upstream EGF receptor. Strain-induced EGFR/ERK signaling relies on mechanosensitive E-cadherin adhesions, as this signaling is disrupted upon genetic modulation of force transduction by the E-cadherin complex. Proximity labeling identified a connection between E-cadherin and ADAM17, an enzyme that mediates the shedding of soluble EGFR ligands. We developed a novel ADAM activity probe to demonstrate that mechanical strain induces ADAM activation, which relays mechanosensitive signaling from E-cadherin adhesions towards EGFR/ERK. Collectively, our data demonstrate how mechanical strain transduced by Ecadherin adhesion modulates the presence of EGFR ligands to regulate downstream ERK activity. Our findings illustrate how mechanical signals and biochemical ligands can operate within a single, linear signaling cascade.
HostingRepository	PRIDE
AnnounceDate	2025-11-18
AnnouncementXML	Submission_2025-11-18_02:13:22.958.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harmjan Vos
SpeciesList	scientific name: Canis familiaris (Dog) (Canis lupus familiaris); NCBI TaxID: NEWT:9615;
ModificationList	biotinylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-26 05:08:45	ID requested
⏵ 1	2025-11-18 02:13:23	announced

10.1126/scisignal.adr7926;

Houtekamer RM, van der Net MC, Vliem MJ, Noordzij TEJC, van Uden L, van Es RM, Sim JY, Deguchi E, Terai K, Hopcroft MA, Vos HR, Pruitt BL, Matsuda M, Pannekoek WJ, Gloerich M, E-cadherin mechanotransduction activates EGFR-ERK signaling in epithelial monolayers by inducing ADAM-mediated ligand shedding. Sci Signal, 18(886):eadr7926(2025) [pubmed]

submitter keyword: E-cadherin force transduction EGFR ligand shedding

Martijn Gloerich
contact affiliation	Center for Molecular Medicine, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands
contact email	M.Gloerich@umcutrecht.nl
lab head
Harmjan Vos
contact affiliation	University Medical Center Utrecht Dept. Molecular Cancer Research
contact email	h.r.vos-3@umcutrecht.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD061223

PRIDE project URI

• PRIDE
  1. PXD061223
     1. Label: PRIDE project
     2. Name: E-cadherin mechanotransduction activates EGFR/ERK signaling by inducing ligand shedding