ARD1 contributes to IKKβ-mediated breast cancer tumorigenesis.

ARD1 contributes to IKKβ-mediated breast cancer tumorigenesis.
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ARD1 有助于 IKK β 介导的乳腺癌肿瘤发生

DOI:
10.1038/s41419-018-0921-2
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发表时间:
2018-08-28
影响因子:
9
通讯作者:
Nie C
Nie C
中科院分区:
生物学1区
文献类型:
--
作者:
Zhang Y;Zhou H;Tao Y;Liu X;Yuan Z;Nie C

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IκB激酶β(IKKβ)的表达促进乳腺癌细胞的生长。同时,IKKβ介导了ARD1的磷酸化和随后的降解。但IKKβ与ARD1在乳腺癌发生中的关系尚未见报道。本研究发现IKKβ不仅直接作用于哺乳动物雷帕霉素靶蛋白(mTOR)的活性,还通过对ARD1的转录后修饰间接作用于mTOR的活性,从而有效促进乳腺癌细胞的生长。ARD1通过稳定结节性硬化症复合物2(TSC 2)诱导自噬来阻止mTOR活性和乳腺癌细胞生长。此外,热休克蛋白70(Hsp70)的乙酰化也有助于ARD1介导的自噬。因此,上游IKKβ可通过介导ARD 1的功能进一步促进乳腺癌的发生。
The expression of IκB kinase β (IKKβ) promotes the growth of breast cancer cells. Meanwhile, IKKβ mediates the phosphorylation and subsequent degradation of arrest-defective protein 1 (ARD1). However, the relationship between IKKβ and ARD1 in the occurrence of breast cancer has not been reported. In this study, we found that IKKβ not only acts directly on mammalian target of rapamycin (mTOR) activity but also indirectly acts on mTOR activity through posttranscriptional modification of ARD1, thereby effectively promoting the growth of breast cancer cells. ARD1 prevents mTOR activity and breast cancer cell growth by stabilizing tuberous sclerosis complex 2 (TSC2) to induce autophagy. Moreover, acetylation of heat shock protein 70 (Hsp70) also contributes to ARD1-mediated autophagy. Therefore, upstream IKKβ can further promote the occurrence of breast cancer by mediating the function of ARD1.
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