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NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth
Panneerselvam Jayabal1, Fuchun Zhou1, Xiufen Lei1
1Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229, USA.
Cell Reports
|July 7, 2021
Summary
Ewing sarcoma cells rely on NELL2 signaling, which inhibits cdc42 and boosts BAF complexes and EWS-FLI1. This pathway regulates chromatin remodeling and cancer cell proliferation.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- BAF chromatin remodeling complexes are crucial in chromatin regulation and cancer.
- Ewing sarcoma is a pediatric cancer driven by the EWS-FLI1 fusion gene.
Purpose of the Study:
- To investigate the role of NELL2 signaling in Ewing sarcoma.
- To elucidate the regulatory mechanisms of BAF complexes in Ewing sarcoma.
Main Methods:
- Analysis of NELL2 signaling pathway components in Ewing sarcoma cells.
- Investigating the interaction between NELL2, Robo3, cdc42, and BAF complexes.
- Identifying distinct Ewing sarcoma cell populations based on NELL2, CD133, and EWS-FLI1 expression.
Main Results:
- Ewing sarcoma cells are dependent on NELL2 autocrine signaling via Robo3.
- NELL2 signaling inhibits cdc42, upregulating BAF complexes and EWS-FLI1 transcription.
- cdc42 acts as a negative regulator of BAF complexes.
- Identified NELL2highCD133highEWS-FLI1high and NELL2lowCD133lowEWS-FLI1low Ewing sarcoma populations.
- NELL2, CD133, and EWS-FLI1 positively regulate each other, enhancing BAF complexes and proliferation.
Conclusions:
- A novel signaling pathway involving NELL2, cdc42, and BAF complexes regulates Ewing sarcoma progression.
- This pathway represents a potential therapeutic target for Ewing sarcoma.
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