Skip to Main content Skip to Navigation
Journal articles

Matrix-bound PAI-1 supports membrane blebbing via RHOA/ROCK1 signaling

Abstract : The microenvironment of a tumor can influence both the morphology and the behavior of cancer cells which, in turn, can rapidly adapt to environmental changes. Increasing evidence points to the involvement of amoeboid cell migration and thus of cell blebbing in the metastatic process; however, the cues that promote amoeboid cell behavior in physiological and pathological conditions have not yet been clearly identified. Plasminogen Activator Inhibitor type-1 (PAI-1) is found in high amount in the microenvironment of aggressive tumors and is considered as an independent marker of bad prognosis. Here we show by immunoblotting, activity assay and immunofluorescence that, in SW620 human colorectal cancer cells, matrix-associated PAI-1 plays a role in the cell behavior needed for amoeboid migration by maintaining cell blebbing, localizing PDK1 and ROCK1 at the cell membrane and maintaining the RhoA/ROCK1/MLC-P pathway activation. The results obtained by modeling PAI-1 deposition around tumors indicate that matrix-bound PAI-1 is heterogeneously distributed at the tumor periphery and that, at certain spots, the elevated concentrations of matrix-bound PAI-1 needed for cancer cells to undergo the mesenchymal-amoeboid transition can be observed. Matrix-bound PAI-1, as a matricellular protein, could thus represent one of the physiopathological requirements to support metastatic formation.
Document type :
Journal articles
Complete list of metadata
Contributor : Frédéric Davesne Connect in order to contact the contributor
Submitted on : Tuesday, June 8, 2021 - 5:24:38 PM
Last modification on : Friday, August 5, 2022 - 10:44:48 AM
Long-term archiving on: : Thursday, September 9, 2021 - 8:23:01 PM


Publisher files allowed on an open archive


Distributed under a Creative Commons Attribution 4.0 International License



Amandine Cartier-Michaud, Michel Malo, Cécile Charrière-Bertrand, Gilles Gadea, Christelle Anguille, et al.. Matrix-bound PAI-1 supports membrane blebbing via RHOA/ROCK1 signaling. PLoS ONE, Public Library of Science, 2012, 7 (2), pp.e32204. ⟨10.1371/journal.pone.0032204⟩. ⟨hal-00677159⟩



Record views


Files downloads