TIMELESS inhibits breast cancer cell invasion and metastasis by down-regulating the expression of MMP9.
TIMELESS inhibits breast cancer cell invasion and metastasis by down-regulating the expression of MMP9.
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TIMELESS通过下调MMP9表达抑制乳腺癌细胞侵袭和转移
DOI：
10.1186/s12935-021-01752-y
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发表时间：
2021-01-11
影响因子：
5.8
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Li B;Mu L;Li Y;Xia K;Yang Y;Aman S;Ahmad B;Li S;Wu H
乳腺癌是导致女性死亡的第一杀手，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还不是很清楚。我们的研究表明，过表达TIMELESS可以显著抑制乳腺癌细胞ZR-75-30的侵袭和转移，并抑制F-actin蛋白的组装。相反，TIMELESS基因的敲低促进了乳腺癌细胞的侵袭和转移。进一步的研究表明，TIMELESS过表达降低了MMP 9的mRNA和蛋白水平。TIMELESS可与p65相互作用，抑制p65与其乙酰转移酶CBP的结合，下调p65的乙酰化水平，从而抑制NF-κB信号通路的激活。综上所述，TIMELESS可能通过抑制p65的乙酰化，抑制NF-κB的活化，从而下调MMP 9的表达，抑制乳腺癌细胞的侵袭和转移。
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.
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影响因子：
11.2
作者：
Boggs AE;Vitolo MI;Whipple RA;Charpentier MS;Goloubeva OG;Ioffe OB;Tuttle KC;Slovic J;Lu Y;Mills GB;Martin SS
通讯作者：
Martin SS
影响因子：
4.6
作者：
Liu Y;Ao X;Jia Z;Bai XY;Xu Z;Hu G;Jiang X;Chen M;Wu H
通讯作者：
Wu H
影响因子：
4.3
作者：
Smith-Roe, Stephanie L.;Patel, Shivani S.;Kaufmann, William K.
通讯作者：
Kaufmann, William K.
影响因子：
11.5
作者：
Reimers, N;Zafrakas, K;Pantel, K
通讯作者：
Pantel, K
影响因子：
14.9
作者：
Lecoq L;Raiola L;Chabot PR;Cyr N;Arseneault G;Legault P;Omichinski JG
通讯作者：
Omichinski JG