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Circadian protein BMAL1 promotes breast cancer cell invasion and metastasis by up-regulating matrix metalloproteinase9 expression
- Source :
- Cancer Cell International, Vol 19, Iss 1, Pp 1-12 (2019), Cancer Cell International
- Publication Year :
- 2019
- Publisher :
- BMC, 2019.
-
Abstract
- Background Metastasis is an important factor in the poor prognosis of breast cancer. As an important core clock protein, brain and muscle arnt-like 1 (BMAL1) is closely related to tumorigenesis. However, the molecular mechanisms that mediate the role of BMAL1 in invasion and metastasis remain largely unknown. In this study, we investigated the BMAL1 may take a crucial effect in the progression of breast cancer cells. Methods BMAL1 and MMP9 expression was measured in breast cell lines. Transwell and scratch wound-healing assays were used to detect the movement of cells and MTT assays and clonal formation assays were used to assess cells’ proliferation. The effects of BMAL1 on the MMP9/NF-κB pathway were examined by western blotting, co-immunoprecipitation and mammalian two-hybrid. Results In our study, it showed that cell migration and invasion were significantly enhanced when overexpressed BMAL1. Functionally, overexpression BMAL1 significantly increased the mRNA and protein level of matrix metalloproteinase9 (MMP9) and improved the activity of MMP9. Moreover, BMAL1 activated the NF-κB signaling pathway by increasing the phosphorylation of IκB and promoted human MMP9 promoter activity by interacting with NF-kB p65, leading to increased expression of MMP9. When overexpressed BMAL1, CBP (CREB binding protein) was recruited to enhance the activity of p65 and further activate the NF-κB signaling pathway to regulate the expression of its downstream target genes, including MMP9, TNFα, uPA and IL8, and then promote the invasion and metastasis of breast cancer cells. Conclusions This study confirmed a new mechanism by which BMAL1 up-regulated MMP9 expression to increase breast cancer metastasis, to provide research support for the prevention and treatment of breast cancer.
- Subjects :
- Cancer Research
endocrine system
MMP9
medicine.disease_cause
lcsh:RC254-282
NF-κB
Metastasis
03 medical and health sciences
0302 clinical medicine
Breast cancer
Invasion
Genetics
medicine
CREB-binding protein
lcsh:QH573-671
biology
lcsh:Cytology
BMAL1
Cell migration
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
body regions
Oncology
030220 oncology & carcinogenesis
Cancer research
biology.protein
Tumor necrosis factor alpha
Signal transduction
Carcinogenesis
Primary Research
Subjects
Details
- Language :
- English
- ISSN :
- 14752867
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cancer Cell International
- Accession number :
- edsair.doi.dedup.....ec92d219b9022b7221abfb1953a78157