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Interaction between BEND5 and RBPJ suppresses breast cancer growth and metastasis via inhibiting Notch signaling.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2022 Jun 27; Vol. 18 (10), pp. 4233-4244. Date of Electronic Publication: 2022 Jun 27 (Print Publication: 2022). - Publication Year :
- 2022
-
Abstract
- High frequent metastasis is the major cause of breast cancer (BC) mortality among women. However, the molecular mechanisms underlying BC metastasis remain largely unknown. Here, we identified six hub BC metastasis driver genes (BEND5, HSD11B1, NEDD9, SAA2, SH2D2A and TNFSF4) through bioinformatics analysis, among which BEND5 is the most significant gene. Low BEND5 expression predicted advanced stage and shorter overall survival in BC patients. Functional experiments showed that BEND5 could suppress BC growth and metastasis in vitro and in vivo . Mechanistically, BEND5 inhibits Notch signaling via directly interacting with transcription factor RBPJ/CSL. BEN domain of BEND5 interacts with the N-terminal domain (NTD) domain of RBPJ, thus preventing mastermind like transcriptional coactivator (MAML) from forming a transcription activation complex with RBPJ. Our study provides a novel insight into regulatory mechanisms underlying Notch signaling and suggests that BEND5 may become a promising target for BC therapy.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Female
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Humans
Immunoglobulin J Recombination Signal Sequence-Binding Protein genetics
Immunoglobulin J Recombination Signal Sequence-Binding Protein metabolism
OX40 Ligand genetics
OX40 Ligand metabolism
Signal Transduction
Transcription Factors genetics
Transcription Factors metabolism
Breast Neoplasms genetics
Breast Neoplasms metabolism
Breast Neoplasms pathology
Receptors, Notch genetics
Receptors, Notch metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 18
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35844785
- Full Text :
- https://doi.org/10.7150/ijbs.70866