Abstract
Breast cancer is the first killer leading to female death, and tumor metastasis is one of the important factors leading to the death of patients, but the specific mechanism of breast cancer metastasis is not very clear at present. Our study showed that overexpression of TIMELESS could significantly inhibit the invasion and metastasis of breast cancer cells ZR-75-30 and the assembly of F-actin protein. On the contrary, knockdown of TIMELESS promoted the invasion and metastasis of breast cancer cells. Further study revealed that TIMELESS overexpression decreased the mRNA and protein levels of MMP9. Furthermore, TIMELESS could interact with p65, leading to repress the association of p65 and its acetyltransferase CBP and down-regulating the acetylation level of p65, which inhibited the activation of NF-κB signal pathway. In conclusion, our research showed that TIMELESS may repress the invasion and metastasis of breast cancer cells via inhibiting the acetylation of p65, inhibiting the activation of NF-κB, thus down-regulating the expression of MMP9, and then inhibiting the invasion and metastasis of breast cancer cells.
Highlights
Breast cancer is one of the most serious threats to women’s health worldwide
Based on the results of KM analysis on patients of basal- TIMELESS inhibited the expression of Matrix metalloproteinase9 (MMP9) like breast cancer, the survival of patients with high MMP9 is a key factor in the process of tumor invasion expression of TIMELESS was significantly higher than and metastasis
TIMELESS repressed MMP9 expression by reducing the activation of NF‐κB As we all know, MMP9 is an important downstream target gene of the NF-κB signaling pathway, so we studied whether TIMELESS regulates MMP9 through the NF-κB signaling pathway
Summary
Its annual average growth rate is about 4% with poor prognosis and the median survival time is only 2–3 years in China, which is a bad situation and closely related to the invasion and metastasis of breast cancer cells [1, 2]. Research on the mechanisms of breast cancer invasion and metastasis will help provide new strategies for clinical diagnosis and treatment. MMP9 is one of the most important members of MMPs family and one of the target genes of NF-κB. It can degrade collagen IV, the main component of the cell basement membrane, which plays an important role in cancer metastasis [5]. MMP9 can take different effects in the process of cell scatter, such as
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