Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A

Huang,Qiuyue; Qin,Shanshan; Yuan,Xiaoning; Zhang,Liang; Ji,Juanli; Liu,Xuewen; Ma,Wenjing; Zhang,Yunfei; Liu,Pengfei; Sun,Zhiting; Zhang,Jingxuan; Liu,Ying

doi:10.3892/or.2017.5667

Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A

Authors:
- Qiuyue Huang
- Shanshan Qin
- Xiaoning Yuan
- Liang Zhang
- Juanli Ji
- Xuewen Liu
- Wenjing Ma
- Yunfei Zhang
- Pengfei Liu
- Zhiting Sun
- Jingxuan Zhang
- Ying Liu
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Affiliations: Laboratory of Molecular Target Therapy of Cancer, Institute of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
Published online on: May 24, 2017 https://doi.org/10.3892/or.2017.5667
Pages: 598-606

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Abstract

We have shown that a novel STAT3 inhibitor arctigenin (Atn) induces significant cytotoxicity in triple-negative breast cancer (TNBC) cells. This study further delineated molecular mechanisms where by Atn triggered cytotoxicity in TNBC cells. We found Atn can also inhibit metastasis in TNBC cells through cancerous inhibitor of protein phosphatase 2A (CIP2A) pathway. CIP2A is an endogenous inhibitor of protein phosphatase 2A (PP2A), which can increase the migration and invasion of various cancer cells. PP2A is a tumor suppressor, which is functionally defective in various cancers. Atn-induced metastasis inhibition was associated with reactivation of PP2A, downregulation of CIP2A and Akt phosphorylation. Silencing CIP2A enhanced Atn-induced metastasis inhibition and apoptosis in TNBCs. Furthermore, ectopic expression of CIP2A or inhibition of PP2A in TNBC cells abolished the effects of Atn. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A, at least in part, promotes the anti-metastasis effect induced by Atn. Our findings disclose the novel therapeutic mechanism of this targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.

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