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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
PubMed

Insights

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.
Keywords:
BAF complexCD133Ewing sarcomaNELL2Robo3cdc42secretome proteomics

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