Oncotarget

Research Papers:

Cullin3 promotes breast cancer cells metastasis and epithelial-mesenchymal transition by targeting BRMS1 for degradation

Xiongwei Huo _, Suoni Li, Tingting Shi, Aili Suo, Zhiping Ruan, Hui Guo and Yu Yao

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Oncotarget. 2015; 6:41959-41975. https://doi.org/10.18632/oncotarget.5999

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Abstract

Xiongwei Huo1, Suoni Li2, Tingting Shi3, Aili Suo3, Zhiping Ruan3, Hui Guo3, Yu Yao3

1Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China

2Department of Oncology, Shaanxi Province Tumor Hospital, Xi'an, Shaanxi, 710061, China

3Department of Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China

Correspondence to:

Yu Yao, e-mail: [email protected]

Keywords: Cullin3, epithelial-mesenchymal transition, invasion, BRMS1, breast cancer

Received: August 23, 2015     Accepted: October 03, 2015     Published: October 16, 2015

ABSTRACT

Metastasis is the leading cause of death in breast cancer (BC) patients. However, until now, the mechanisms of BC metastasis remain elusive. Cullin3 is a highly conserved Cullin family member present in the genomes of all eukaryotes, which has been proposed as an oncogene in many types of tumors; however, its role and underlying mechanisms in BC remain unclear. Here we show that Cullin3 is elevated in BC and its expression level is positively correlated with metastasis. Overexpression of Cullin3 in BC cells increased proliferation, epithelial-mesenchymal transition, migration and invasion in vitro, and enhanced tumorigenic and metastatic capacities in vivo. In contrast, silencing Cullin3 in aggressive and invasive BC cells inhibited these processes. Mechanistically, we found Cullin3 exerts its function through promoting BRMS1 protein degradation, which was associated with EMT, migration and invasion. BRMS1 overexpression blocked Cullin3-driven EMT, and metastasis. Our results, for the first time, portray a pivotal role of Cullin3 in stimulating metastatic behaviors of BC cells. Targeting Cullin3 may thus be a useful strategy to impede BC cell invasion and metastasis.


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