| RRC ID |
66165
|
| 著者 |
Jayabal P, Zhou F, Lei X, Ma X, Blackman B, Weintraub ST, Houghton PJ, Shiio Y.
|
| タイトル |
NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth.
|
| ジャーナル |
Cell Rep
|
| Abstract |
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.
|
| 巻・号 |
36(1)
|
| ページ |
109254
|
| 公開日 |
2021-7-6
|
| DOI |
10.1016/j.celrep.2021.109254
|
| PII |
S2211-1247(21)00619-7
|
| PMID |
34233189
|
| PMC |
PMC8312579
|
| MeSH |
AC133 Antigen / metabolism
Actins / metabolism
Animals
Cell Line, Tumor
Cell Proliferation
Chromatin Assembly and Disassembly
Down-Regulation
Gene Expression Regulation, Neoplastic
Humans
Mice, SCID
Multiprotein Complexes / metabolism*
Nerve Tissue Proteins / metabolism*
Oncogene Proteins, Fusion / metabolism
Phenotype
Polymerization
Protein Subunits / metabolism
Proteomics
Proto-Oncogene Protein c-fli-1 / metabolism
RNA-Binding Protein EWS / metabolism
Receptors, Cell Surface / metabolism
Sarcoma, Ewing / genetics
Sarcoma, Ewing / metabolism*
Sarcoma, Ewing / pathology*
Signal Transduction*
Up-Regulation
cdc42 GTP-Binding Protein / metabolism*
|
| IF |
8.109
|
| リソース情報 |
| ヒト・動物細胞 |
Aska-SS(RCB3576) |
