Cadherin-11 contributes to the heterogenous and dynamic Wnt-Wnt-ß-catenin pathway activation in Ewing sarcoma.
PLoS One
; 19(6): e0305490, 2024.
Article
in En
| MEDLINE
| ID: mdl-38875295
ABSTRACT
Ewing sarcoma is the second most common bone cancer in children, and while patients who present with metastatic disease at the time of diagnosis have a dismal prognosis. Ewing sarcoma tumors are driven by the fusion gene EWS/Fli1, and while these tumors are genetically homogenous, the transcriptional heterogeneity can lead to a variety of cellular processes including metastasis. In this study, we demonstrate that in Ewing sarcoma cells, the canonical Wnt/ß-Catenin signaling pathway is heterogeneously activated in vitro and in vivo, correlating with hypoxia and EWS/Fli1 activity. Ewing sarcoma cells predominantly express ß-Catenin on the cell membrane bound to CDH11, which can respond to exogenous Wnt ligands leading to the immediate activation of Wnt/ß-Catenin signaling within a tumor. Knockdown of CDH11 leads to delayed and decreased response to exogenous Wnt ligand stimulation, and ultimately decreased metastatic propensity. Our findings strongly indicate that CDH11 is a key component of regulating Wnt//ß-Catenin signaling heterogeneity within Ewing sarcoma tumors, and is a promising molecular target to alter Wnt//ß-Catenin signaling in Ewing sarcoma patients.
Full text:
1
Database:
MEDLINE
Main subject:
Sarcoma, Ewing
/
Cadherins
/
Beta Catenin
/
Wnt Signaling Pathway
Limits:
Animals
/
Humans
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2024
Type:
Article
Affiliation country:
United States