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

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, matrixassociated 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. Citation: Cartier-Michaud A, Malo M, Charrière-Bertrand C, Gadea G, Anguille C, et al. (2012) Matrix-Bound PAI-1 Supports Cell Blebbing via RhoA/ROCK1 Signaling. PLoS ONE 7(2): e32204. doi:10.1371/journal.pone.0032204 Editor: Gordon Langsley, Institut national de la santé et de la recherche médicale Institut Cochin, France Received March 19, 2011; Accepted January 24, 2012; Published February 21, 2012 Copyright: 2012 Cartier-Michaud et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors are grateful to the following for their financial support: IBISC (grant ‘‘Action Incitative’’), Evry Genopole (grant ‘‘Aide à l’acquisition d’équipement semi-lourd’’), the CNRS ACI Program ‘‘Complexité du vivant’’ (grant # 050009DR11), and the GDR 2647 ‘‘STIC-Santé’’ CNRS/Inserm. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: georgia.barlovatz@ibisc.fr . These authors contributed equally to this work.