Cargando…
NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth
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 r...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312579/ https://www.ncbi.nlm.nih.gov/pubmed/34233189 http://dx.doi.org/10.1016/j.celrep.2021.109254 |
_version_ | 1783729173110456320 |
---|---|
author | Jayabal, Panneerselvam Zhou, Fuchun Lei, Xiufen Ma, Xiuye Blackman, Barron Weintraub, Susan T. Houghton, Peter J. Shiio, Yuzuru |
author_facet | Jayabal, Panneerselvam Zhou, Fuchun Lei, Xiufen Ma, Xiuye Blackman, Barron Weintraub, Susan T. Houghton, Peter J. Shiio, Yuzuru |
author_sort | Jayabal, Panneerselvam |
collection | PubMed |
description | 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 NELL2(high)CD133(high)EWS-FLI1(high) and NELL2(low)CD133(low)EWS-FLI1(low) 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. |
format | Online Article Text |
id | pubmed-8312579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-83125792021-07-26 NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth Jayabal, Panneerselvam Zhou, Fuchun Lei, Xiufen Ma, Xiuye Blackman, Barron Weintraub, Susan T. Houghton, Peter J. Shiio, Yuzuru Cell Rep Article 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 NELL2(high)CD133(high)EWS-FLI1(high) and NELL2(low)CD133(low)EWS-FLI1(low) 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. 2021-07-06 /pmc/articles/PMC8312579/ /pubmed/34233189 http://dx.doi.org/10.1016/j.celrep.2021.109254 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Jayabal, Panneerselvam Zhou, Fuchun Lei, Xiufen Ma, Xiuye Blackman, Barron Weintraub, Susan T. Houghton, Peter J. Shiio, Yuzuru NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth |
title | NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth |
title_full | NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth |
title_fullStr | NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth |
title_full_unstemmed | NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth |
title_short | NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth |
title_sort | nell2-cdc42 signaling regulates baf complexes and ewing sarcoma cell growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312579/ https://www.ncbi.nlm.nih.gov/pubmed/34233189 http://dx.doi.org/10.1016/j.celrep.2021.109254 |
work_keys_str_mv | AT jayabalpanneerselvam nell2cdc42signalingregulatesbafcomplexesandewingsarcomacellgrowth AT zhoufuchun nell2cdc42signalingregulatesbafcomplexesandewingsarcomacellgrowth AT leixiufen nell2cdc42signalingregulatesbafcomplexesandewingsarcomacellgrowth AT maxiuye nell2cdc42signalingregulatesbafcomplexesandewingsarcomacellgrowth AT blackmanbarron nell2cdc42signalingregulatesbafcomplexesandewingsarcomacellgrowth AT weintraubsusant nell2cdc42signalingregulatesbafcomplexesandewingsarcomacellgrowth AT houghtonpeterj nell2cdc42signalingregulatesbafcomplexesandewingsarcomacellgrowth AT shiioyuzuru nell2cdc42signalingregulatesbafcomplexesandewingsarcomacellgrowth |