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

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 proteo...

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Autores principales: Jiang, Hong-Lin, Sun, He-Fen, Gao, Shui-Ping, Li, Liang-Dong, Hu, Xin, Wu, Jiong, Jin, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599274/
https://www.ncbi.nlm.nih.gov/pubmed/25970785
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author Jiang, Hong-Lin
Sun, He-Fen
Gao, Shui-Ping
Li, Liang-Dong
Hu, Xin
Wu, Jiong
Jin, Wei
author_facet Jiang, Hong-Lin
Sun, He-Fen
Gao, Shui-Ping
Li, Liang-Dong
Hu, Xin
Wu, Jiong
Jin, Wei
author_sort Jiang, Hong-Lin
collection PubMed
description 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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spelling pubmed-45992742015-10-26 Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-β/SMAD signaling Jiang, Hong-Lin Sun, He-Fen Gao, Shui-Ping Li, Liang-Dong Hu, Xin Wu, Jiong Jin, Wei Oncotarget Research Paper 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. Impact Journals LLC 2015-04-19 /pmc/articles/PMC4599274/ /pubmed/25970785 Text en Copyright: © 2015 Jiang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Jiang, Hong-Lin
Sun, He-Fen
Gao, Shui-Ping
Li, Liang-Dong
Hu, Xin
Wu, Jiong
Jin, Wei
Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-β/SMAD signaling
title Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-β/SMAD signaling
title_full Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-β/SMAD signaling
title_fullStr Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-β/SMAD signaling
title_full_unstemmed Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-β/SMAD signaling
title_short Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-β/SMAD signaling
title_sort loss of rab1b promotes triple-negative breast cancer metastasis by activating tgf-β/smad signaling
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599274/
https://www.ncbi.nlm.nih.gov/pubmed/25970785
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