Autor: |
Aran Park, Sanghyuk Choi, Jungbeom Do, Youngjae Kim, Kyung-Sup Kim, Eunjin Koh, Ki-Sook Park |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
|
Zdroj: |
Cell Death Discovery, Vol 10, Iss 1, Pp 1-15 (2024) |
Druh dokumentu: |
article |
ISSN: |
2058-7716 |
DOI: |
10.1038/s41420-023-01793-4 |
Popis: |
Abstracts Mesenchymal 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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|