Research Papers:

TIPE3 protein promotes breast cancer metastasis through activating AKT and NF-κB signaling pathways

Kaili Lian, Chao Ma, Chunyan Hao, Yan Li, Na Zhang, Youhai H. Chen and Suxia Liu _

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Oncotarget. 2017; 8:48889-48904. https://doi.org/10.18632/oncotarget.16522

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Kaili Lian1, Chao Ma2, Chunyan Hao2, Yan Li1, Na Zhang1, Youhai H. Chen3 and Suxia Liu1

1Department of Immunology, Shandong University School of Medicine, Ji’nan, P.R. China

2Department of Pathology, Shandong University School of Medicine, Ji’nan, P.R. China

3Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

Correspondence to:

Suxia Liu, email: [email protected]

Keywords: TNFAIP8L3, breast cancer, metastasis, AKT, NF-κB

Received: October 07, 2016     Accepted: March 15, 2017     Published: March 23, 2017


TIPE3 (TNFAIP8L3) is the transfer protein of phosphoinositide second messengers that promote cancer. Its role in breast cancer has not been evaluated. We report here that TIPE3 protein was significantly upregulated in human breast cancer tissues as compared with adjacent non-tumor tissues from the same patients. The level of TIPE3 protein in invasive ductal carcinoma was significant higher than that in ductal carcinoma in situ (DCIS), and the level of TIPE3 in lymphatic metastasized carcinoma was higher than that in invasive ductal carcinoma from the same patients. Additionally, the level of TIPE3 protein was positively correlated with the level of human epidermal growth factor receptor 2 (HER-2), and TIPE3 expression was significantly higher in high-invasive breast cancer cell lines than that in low-invasive cell lines. Importantly, TIPE3 knockdown in breast cancer cells inhibited cell proliferation, migration, and invasion in vitro, whereas TIPE3 overexpression had the opposite effect. In mice, TIPE3 expression significantly promoted the metastasis of breast cancer cells. TIPE3 expression also increased the level of MMP2 and uPA, and the activation of the AKT and NF-κB signaling pathways. These results demonstrate that TIPE3 may promote breast cancer growth and metastasis through AKT and NF-κB, and may serve as a potential biomarker for breast cancer metastasis.

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