Oncotarget

Research Papers:

Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-β/SMAD signaling

Hong-Lin Jiang, He-Fen Sun, Shui-Ping Gao, Liang-Dong Li, Xin Hu, Jiong Wu and Wei Jin _

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Oncotarget. 2015; 6:16352-16365. https://doi.org/10.18632/oncotarget.3877

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Abstract

Hong-Lin Jiang1,2,*, He-Fen Sun1,2,*, Shui-Ping Gao1,2, Liang-Dong Li1,2, Xin Hu1, Jiong Wu1,2 and Wei Jin1,2

1 Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China

2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

* These authors have contributed equally to this work

Correspondence to:

Wei Jin, email:

Jiong Wu, email:

Keywords: RAB1B; triple-negative; metastatic breast cancer; TGF-β/SMAD signaling

Received: January 23, 2015 Accepted: April 03, 2015 Published: April 19, 2015

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype associated with a poor prognosis. The mechanism involved in TNBC progression remains largely unknown. To date, there are no effective therapeutic targets for this tumor subtype. In this study, by performing quantitative proteomic analyses in highly metastatic and parental breast cancer cell line, we found that RAB1B, a member of the RAS oncogene family, was significantly down-regulated in highly metastatic breast cancer cells. Moreover, down-regulation of RAB1B was also found to promote the proliferation and migration of TNBC cells in vitro and in vivo. Mechanistically, loss of RAB1B resulted in elevated expression of TGF-β receptor 1 (TβR1) through decreased degradation of ubiquitin, increased levels of phosphorylated SMAD3 and TGF-β-induced epithelial-mesenchymal transition (EMT). Furthermore, low RAB1B expression correlated with poor prognosis in breast cancer patients. Taken together, our findings reveal that RAB1B acts as a metastasis suppressor in TNBC by regulating the TGF-β/SMAD signaling pathway and RAB1B may serve as a novel biomarker of prognosis and the response to anti-tumor therapeutics for patients with TNBC.


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