NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth

Panneerselvam Jayabal, Fuchun Zhou, Xiufen Lei, Xiuye Ma, Barron Blackman, Susan T. Weintraub, Peter J. Houghton, Yuzuru Shiio

Producción científica: Articlerevisión exhaustiva

6 Citas (Scopus)


BAF chromatin remodeling complexes play important roles in chromatin regulation and cancer. Here, we report that Ewing sarcoma cells are dependent on the autocrine signaling mediated by NELL2, a secreted glycoprotein that has been characterized as an axon guidance molecule. NELL2 uses Robo3 as the receptor to transmit critical growth signaling. NELL2 signaling inhibits cdc42 and upregulates BAF complexes and EWS-FLI1 transcriptional output. We demonstrate that cdc42 is a negative regulator of BAF complexes, inducing actin polymerization and complex disassembly. Furthermore, we identify NELL2highCD133highEWS-FLI1high and NELL2lowCD133lowEWS-FLI1low populations in Ewing sarcoma, which display phenotypes consistent with high and low NELL2 signaling, respectively. We show that NELL2, CD133, and EWS-FLI1 positively regulate each other and upregulate BAF complexes and cell proliferation in Ewing sarcoma. These results reveal a signaling pathway regulating critical chromatin remodeling complexes and cancer cell proliferation.

Idioma originalEnglish (US)
Número de artículo109254
PublicaciónCell Reports
EstadoPublished - jul 6 2021

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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