ZO-1 regulates the migration of mesenchymal stem cells in cooperation with α-catenin in response to breast tumor cells

Abstract

AbstractsMesenchymal stem cells are recruited from the bone marrow into breast tumors, contributing to the creation of a tumor microenvironment that fosters tropism for breast tumors. However, the intrinsic mechanisms underlying the recruitment of bone marrow-derived mesenchymal stem cells (MSCs) into the breast tumor microenvironment are still under investigation. Our discoveries identified zonula occludens-1 (ZO-1) as a specific intrinsic molecule that plays a vital role in mediating the collective migration of MSCs towards breast tumor cells and transforming growth factor beta (TGF-β), which is a crucial factor secreted by breast tumor cells. Upon migration in response to MDA-MB-231 cells and TGF-β, MSCs showed increased formation of adherens junction-like structures (AJs) expressing N-cadherin and α-catenin at their cell-cell contacts. ZO-1 was found to be recruited into the AJs at the cell-cell contacts between MSCs. Additionally, ZO-1 collaborated with α-catenin to regulate AJ formation, dependently on the SH3 and GUK domains of the ZO-1 protein. ZO-1 knockdown led to the impaired migration of MSCs in response to the stimuli and subsequent downregulation of AJs formation at the cell-cell contacts during MSCs migration. Overall, our study highlights the novel role of ZO-1 in guiding MSC migration towards breast tumor cells, suggesting its potential as a new strategy for controlling and re-engineering the breast tumor microenvironment.

Cadherin‐6 is a novel mediator for the migration of mesenchymal stem cells to glioblastoma cells in response to stromal cell‐derived factor‐1

“…Proteins were resolved on SDS/PAGE. Western blotting of proteins in the cell lysate was performed using standard procedures [ 19 ]. Primary antibodies against anticadherin‐6 (1 : 1000; R&D Systems, Minneapolis, MN, USA) and α‐tubulin (1 : 30 000–1 : 50 000, Sigma‐Aldrich, St. Louis, MO, USA) were used.…”

“…Three‐dimensional migration was performed following the procedures described in the previous study [ 19 ]. A suspension containing MSCs transfected with cadherin‐6 siRNA or the control siRNA was prepared.…”