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ARD1 contributes to IKK?-mediated breast cancer tumorigenesis.

ABSTRACT: The expression of I?B kinase ? (IKK?) promotes the growth of breast cancer cells. Meanwhile, IKK? mediates the phosphorylation and subsequent degradation of arrest-defective protein 1 (ARD1). However, the relationship between IKK? and ARD1 in the occurrence of breast cancer has not been reported. In this study, we found that IKK? 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 IKK? can further promote the occurrence of breast cancer by mediating the function of ARD1.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6113314 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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ARD1 contributes to IKKβ-mediated breast cancer tumorigenesis.

Zhang Yu Y Zhou Hang H Tao Yongjun Y Liu Xingyu X Yuan Zhu Z Nie Chunlai C

Cell death & disease 20180828 9

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, ther ...[more]

PMID: 30154412

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