Format:
26
ISSN:
2211-1247
Content:
Ewing sarcoma (EwS) is a highly aggressive tumor of bone and soft tissues that mostly affects children and adolescents. The pathognomonic oncofusion EWSR1::FLI1 transcription factor drives EwS by orchestrating an oncogenic transcription program through de novo enhancers. By integrative analysis of thousands of transcriptomes representing pan-cancer cell lines, primary cancers, metastasis, and normal tissues, we identify a 32-gene signature (ESS32 [Ewing Sarcoma Specific 32]) that stratifies EwS from pan-cancer. Among the ESS32, LOXHD1, encoding a stereociliary protein, is the most highly expressed gene through an alternative transcription start site. Deletion or silencing of EWSR1::FLI1 bound upstream de novo enhancer results in loss of the LOXHD1 short isoform, altering EWSR1::FLI1 and HIF1α pathway genes and resulting in decreased proliferation/invasion of EwS cells. These observations implicate LOXHD1 as a biomarker and a determinant of EwS metastasis and suggest new avenues for developing LOXHD1-targeted drugs or cellular therapies for this deadly disease.
Note:
Gesehen am 03.08.2022
In:
Cell reports, Maryland Heights, MO : Cell Press, 2012, 39(2022), 11, Artikel-ID 110971, Seite 1-26, 2211-1247
In:
volume:39
In:
year:2022
In:
number:11
In:
elocationid:110971
In:
pages:1-26
In:
extent:26
Language:
English
DOI:
10.1016/j.celrep.2022.110971
URL:
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