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Copy number amplification of ENSA promotes the progression of triple-negative breast cancer via cholesterol biosynthesis.
- Source :
-
Nature communications [Nat Commun] 2022 Feb 10; Vol. 13 (1), pp. 791. Date of Electronic Publication: 2022 Feb 10. - Publication Year :
- 2022
-
Abstract
- Copy number alterations (CNAs) are pivotal genetic events in triple-negative breast cancer (TNBC). Here, our integrated copy number and transcriptome analysis of 302 TNBC patients reveals that gene alpha-endosulfine (ENSA) exhibits recurrent amplification at the 1q21.3 region and is highly expressed in TNBC. ENSA promotes tumor growth and indicates poor patient survival in TNBC. Mechanistically, we identify ENSA as an essential regulator of cholesterol biosynthesis in TNBC that upregulates the expression of sterol regulatory element-binding transcription factor 2 (SREBP2), a pivotal transcription factor in cholesterol biosynthesis. We confirm that ENSA can increase the level of p-STAT3 (Tyr705) and activated STAT3 binds to the promoter of SREBP2 to promote its transcription. Furthermore, we reveal the efficacy of STAT3 inhibitor Stattic in TNBC with high ENSA expression. In conclusion, the amplification of ENSA at the 1q21.3 region promotes TNBC progression and indicates sensitivity to STAT3 inhibitors.<br /> (© 2022. The Author(s).)
- Subjects :
- Animals
Cell Line
Gene Knockdown Techniques
Humans
Intercellular Signaling Peptides and Proteins genetics
Mice
Mice, Inbred NOD
Mice, SCID
STAT3 Transcription Factor metabolism
Sterol Regulatory Element Binding Protein 2
Transcriptome
Up-Regulation
Cholesterol biosynthesis
DNA Copy Number Variations
Gene Expression Regulation, Neoplastic
Intercellular Signaling Peptides and Proteins metabolism
Triple Negative Breast Neoplasms genetics
Triple Negative Breast Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 35145111
- Full Text :
- https://doi.org/10.1038/s41467-022-28452-z