Restoration of Arpin suppresses aggressive phenotype of breast cancer cells

Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Yi Li, Jiliang Qiu, Ting Pang, Zhixing Guo, Yonghui Su, Qingan Zeng, Xuexia Zhang
Arpin, a negative regulator of the actin-related protein-2/3 (Arp2/3) complex, is downregulated and predicts poor prognosis in breast cancer patients. However, its biological relevance in breast cancer is still unclear. This study was conducted to investigate the roles of Arpin in breast cancer growth and invasion. We overexpressed Arpin expression in MCF-7 and MDA-MB-231 breast cancer cells and examined the effects of restoration of Arpin on cell proliferation, colony formation, cell cycle distribution, invasion in vitro and tumorigenesis in vivo. The related molecular mechanism(s) was determined. It was found that ectopic expression of Arpin significantly decreased cell proliferation, colony formation, and tumorigenicity. Flow cytometric analysis showed that overexpression of Arpin significantly increased the percentage of G0/G1-phase cells and decreased the percentage of S-phase cells. Moreover, restoration of Arpin impaired the invasiveness of breast cancer cells, as determined by Transwell invasion assays. Mechanistically, overexpression of Arpin inhibited the phosphorylation of Akt in breast cancer cells. Co-expression of a constitutively active form of Akt blunted the suppression of cell proliferation and invasion by Arpin. Taken together, we provide evidence that Arpin acts as a tumor suppressor in breast cancer, which is associated with inhibition of Akt signaling. Restoration of Arpin may represent a promising therapeutic strategy against breast cancer progression.



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