Study on the influence of matrix PAI-1 on the regulation of Mesenchymal-Amoeboid transition of cancer cells
type: Dataset
description: The Mesenchymal-Amoeboid transition (MAT) is required for metastatic escape, however it has not been associated with a precise physiopathological requirement yet. PAI-1, type-1 plasminogen activator inhibitor, is a tumor matrix molecule considered as marker of bad prognosis and found in high amount in the most aggressive tumors. We show that, in its activated matrix form, PAI-1 is able to maintain, in time and with concentration-dependence, the amoeboid morphology of colorectal and mammary cancer cells, and that this one is associated with a weak integrin-independant adhesion, an amoeboid migration and the activation of RhoA/ROCK-1/MLC-P pathway. The involved molecular mechanism has been partially underlined: we show that immobilization of PAI-1 and its link with uPA are essential, and we assume that the membrane receptor uPAR participates in the transmission of signals maintaining activated the RhoA/ROCK-1/MLC-P pathway. The compatibility of matrix PAI-1 effects towards the main signaling pathways involved in MAT regulation is established in silico with a method based on the modeling of interaction network dynamics. All this results enable for the first time to characterize a matrix physiopathological situation supporting MAT; and although the matrix form of PAI-1 has not been revealed all its secrets yet, it seems to be an interesting therapeutic target.
issued: 2026-05-09T07:00:35.543650
language: fr
modified: 2026-05-09T07:00:35.543655
contact point: Organization
  fn: CCSD
keyword: amoeboid-migration
keyword: echappement-metastasique
keyword: infoeu-reposemanticsdoctoralthesis
keyword: mat
keyword: metastatic-escape
keyword: microenvironnement
keyword: migration-amiboide
keyword: pai-1
keyword: sdvbclife-sciences-q-biocellular-biology
keyword: theses
landing page: https://theses.hal.science/tel-00875713

Study on the influence of matrix PAI-1 on the regulation of Mesenchymal-Amoeboid transition of cancer cells
type: Distribution
format: HTML
issued: 2026-05-09T07:00:35.550276
modified: 2026-05-09T07:00:35.533144
access URL: https://theses.hal.science/tel-00875713

test_moissonnage_selune
type: Agent