Matrix-bound PAI-1 supports cell blebbing via RhoA/ROCK1 signaling.

PloS One
Amandine Cartier-MichaudGeorgia Barlovatz-Meimon

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 obs...Continue Reading

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Citations

Mar 5, 2014·Asian Journal of Andrology·Samantha MorleyMichael R Freeman
Jan 19, 2013·Acta Biotheoretica·Annick Lesne
Nov 19, 2015·Pflügers Archiv : European journal of physiology·Shun WatanabeTsuneo Kobayashi
Nov 4, 2017·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Jelena MilenkovicEdita Miljkovic
Apr 24, 2016·Cellular Oncology (Dordrecht)·Luis Antonio Flores-LópezLuis Arturo Baiza-Gutman
Dec 18, 2013·Molecular and Cellular Biochemistry·Yuko TakaharaTakeshi Senga
Nov 20, 2013·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jelena Grahovac, Alan Wells
Oct 22, 2020·Nature Communications·Irene Rodriguez-HernandezVictoria Sanz-Moreno
Oct 21, 2020·Translational Oncology·Jia-Shun WuXin-Hua Liang
May 18, 2021·The Journal of Investigative Dermatology·Yu-Ju TsengHong-Tai Tzeng

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Methods Mentioned

BETA
electrophoresis
confocal microscopy

Software Mentioned

Amira
AxioVision
GraphPad
Mathematica
Plot Profile
ImageJ
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