Back to Search
Start Over
RelB sustains endocrine resistant malignancy: an insight of noncanonical NF-κB pathway into breast Cancer progression
- Source :
- Cell Communication and Signaling, Vol 18, Iss 1, Pp 1-17 (2020), Cell Communication and Signaling : CCS
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Background The activation of the NF-κB pathway plays a crucial role in the progression of breast cancer (BCa) and also involved in endocrine therapy resistance. On the contrary to the canonical NF-κB pathway, the effect of the noncanonical NF-κB pathway in BCa progression remains elusive. Methods BCa tumor tissues and the corresponding cell lines were examined to determine the correlation between RelB and the aggressiveness of BCa. RelB was manipulated in BCa cells to examine whether RelB promotes cell proliferation and motility by quantitation of apoptosis, cell cycle, migration, and invasion. RNA-Seq was performed to identify the critical RelB-regulated genes involved in BCa metastasis. Particularly, RelB-regulated MMP1 transcription was verified using luciferase reporter and ChIP assay. Subsequently, the effect of RelB on BCa progression was further validated using BCa mice xenograft models. Results RelB uniquely expresses at a high level in aggressive BCa tissues, particularly in triple-negative breast cancer (TNBC). RelB promotes BCa cell proliferation through increasing G1/S transition and/or decreasing apoptosis by upregulation of Cyclin D1 and Bcl-2. Additionally, RelB enhances cell mobility by activating EMT. Importantly, RelB upregulates bone metastatic protein MMP1 expression through binding to an NF-κB enhancer element located at the 5′-flanking region. Accordingly, in vivo functional validation confirmed that RelB deficiency impairs tumor growth in nude mice and inhibits lung metastasis in SCID mice.
- Subjects :
- lcsh:Medicine
Apoptosis
Biochemistry
Metastasis
RelB
EMT
chemistry.chemical_compound
Cell Movement
Cancer progression and breast cancer
skin and connective tissue diseases
Mice, Inbred BALB C
0303 health sciences
lcsh:Cytology
RELB
Cell Cycle
030302 biochemistry & molecular biology
NF-kappa B
Cell cycle
Up-Regulation
Gene Expression Regulation, Neoplastic
Disease Progression
Female
Matrix Metalloproteinase 1
Signal Transduction
Epithelial-Mesenchymal Transition
Cell Survival
Mice, Nude
Bone Neoplasms
Breast Neoplasms
Biology
Models, Biological
03 medical and health sciences
Cyclin D1
Downregulation and upregulation
Cell Line, Tumor
medicine
Animals
Humans
Neoplasm Invasiveness
RNA, Messenger
lcsh:QH573-671
Molecular Biology
Cell Proliferation
Cell growth
Research
Transcription Factor RelB
lcsh:R
Reproducibility of Results
NF-κB
Cell Biology
medicine.disease
Hormones
chemistry
Drug Resistance, Neoplasm
Cancer research
MMP1
Subjects
Details
- ISSN :
- 1478811X
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Cell Communication and Signaling
- Accession number :
- edsair.doi.dedup.....a4115d2d322b04bd34038c86f4858aa5