Non-classical Notch signaling by MDA-MB-231 breast cancer cell-derived small extracellular vesicles promotes malignancy in poorly invasive MCF-7 cells.

Fecha de publicación: 13/01/2022 Fecha Ahead of Print: 13/01/2022

Autores de IIS La Fe

Hernán González King Garibotti

Autor
Sandra Tejedor Gascón

Autor
María Ciria Calduch

Autor
Marta Gil Barrachina

Autor
Rafael Sánchez Sánchez

Autor
Pilar Sepúlveda Sanchis

Autor
Nahuel Aquiles Garcia

Autor

Participantes ajenos a IIS La Fe

Soriano-Navarro, Mario

Grupos

Regeneración y Trasplante Cardíaco

Leader

Pilar Sepúlveda Sanchis

Abstract

Aberrant Notch signaling is implicated in breast cancer progression, and recent studies have demonstrated links between the Notch pathway components Notch1 and Notch1 intracellular domain (N1ICD) with poor clinical outcomes. Growing evidence suggests that Notch signaling can be regulated by small extracellular vesicles (SEVs). Here, we used breast cancer cell models to examine whether SEVs are involved in functional Notch signaling. We found that Notch components are packaged into MDA-MB-231- and MCF-7-derived SEVs, although higher levels of N1ICD were detected in SEVs from the more aggressive MDA-MB-231 cell line than from poorly invasive MCF-7 cells. SEV-Notch components were functional, as SEVs cargo from MDA-MB-231 cells induced the expression of Notch target genes in MCF-7 cells and triggered a more invasive and proliferative phenotype concomitant with the acquisition of mesenchymal features. Neutralization of the N1ICD cargo in MDA-MB-231-derived SEVs significantly reduced their potential to enhance the aggressiveness of MCF-7 cells in vitro and in a xenograft model. Overall, our results indicate that a SEV-mediated non-classical pathway of Notch signal transduction in breast cancer models bypasses the need for classical ligand-receptor interactions, which may have important implications in cancer.

Datos de la publicación

ISSN/ISSNe:: 0929-1903, 1476-5500
Tipo:: Article
Páginas:: 1056-1069
DOI:: 10.1038/s41417-021-00411-8
Factor de Impacto:: 1,207 SCImago ℠
Cuartil:: Q2 SCImago ℠

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Métricas

Filiaciones

Gonzalez-King, Hernan:: Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
Tejedor, Sandra:: Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
Ciria, Maria:: Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
Gil-Barrachina, Marta:: Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
Soriano-Navarro, Mario:: Electron Microscopy Core Facility, Centro de Investigación Príncipe Felipe, Valencia, Spain
Sanchez-Sanchez, Rafael:: Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
Sepulveda, Pilar:: Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria la Fe, Valencia, Spain.
Garcia, Nahuel A.:: Gecorp, Buenos Aires, Argentina.