永恒蛋白通过下调基质金属蛋白酶9的表达来抑制乳腺癌细胞的侵袭和转移。
TIMELESS inhibits breast cancer cell invasion and metastasis by down-regulating the expression of MMP9.
作者信息
Li Bowen, Mu Liying, Li Yanan, Xia Kangkai, Yang Yuxi, Aman Sattout, Ahmad Bashir, Li Shujing, Wu Huijian
机构信息
School of Bioengineering & Key Laboratory of Protein Modification and Disease, Liaoning Province, Dalian University of Technology, 2 Ling Gong Road, Dalian, 116024, Liaoning, China.
出版信息
Cancer Cell Int. 2021 Jan 11;21(1):38. doi: 10.1186/s12935-021-01752-y.
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.
乳腺癌是导致女性死亡的首要杀手，肿瘤转移是导致患者死亡的重要因素之一，但目前乳腺癌转移的具体机制尚不完全清楚。我们的研究表明，TIMELESS的过表达可显著抑制乳腺癌细胞ZR-75-30的侵袭和转移以及F-肌动蛋白的组装。相反，敲低TIMELESS可促进乳腺癌细胞的侵袭和转移。进一步研究发现，TIMELESS的过表达降低了MMP9的mRNA和蛋白水平。此外，TIMELESS可与p65相互作用，导致p65与其乙酰转移酶CBP的结合受到抑制，并下调p65的乙酰化水平，从而抑制NF-κB信号通路的激活。总之，我们的研究表明，TIMELESS可能通过抑制p65的乙酰化、抑制NF-κB的激活，从而下调MMP9的表达，进而抑制乳腺癌细胞的侵袭和转移。
Zotero 插件