Oncotarget

Research Papers:

Overexpression of 14-3-3θ promotes tumor metastasis and indicates poor prognosis in breast carcinoma

Nanlin Li _, Hui Wang, Fan Jing, Chao Tong, Jixin Yang, Hongliang Wei, Jun Yi and Rui Ling

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Oncotarget. 2014; 5:249-257. https://doi.org/10.18632/oncotarget.1502

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Abstract

Nanlin Li1,*, Hui Wang1,*, Jing Fan1, Chao Tong1, Jixin Yang1, Hongliang Wei1, Jun Yi1, Rui Ling1

1 Department of Vascular and Endocrine Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China

* These authors contributed equally to the work

Correspondence:

Rui Ling, email:

Nanlin Li, email:

Keywords: 14-3-3θ, Breast Cancer, Metastasis, Prognosis

Received: October 14, 2013 Accepted: December 3, 2013 Published: December 5, 2013

Abstract

An isoform of the 14-3-3 protein family, 14-3-3θ has been linked with tumor cell proliferation and apoptosis. However, the role of 14-3-3θ in the progression of breast cancer remains unknown. Here, we report that 14-3-3θ plays a critical role in breast cancer metastasis and prognosis. The expression of 14-3-3θ was markedly higher in breast cancer tissues compared to adjacent normal tissues. A hospital-based study cohort of 216 breast cancer patients was evaluated in this study. The level of 14-3-3θ expression was determined and correlated based upon tumor clinicopathological features, disease-free survival, and overall survival. We found that overexpression of 14-3-3θ was correlated with advanced TNM stage (P < 0.05), lymph node metastasis (P < 0.05), and ER negative status (P < 0.05). Breast cancer patients with high 14-3-3θ expression had a shorter overall survival and a higher rate of recurrence than those with low 14-3-3θ expression. Additionally, knockdown of 14-3-3θ expression in breast cancer cells inhibited metastasis in vitro. Similarly, an in vivo assay showed that 14-3-3θ knockdown dramatically suppressed the growth of breast cancer xenografts and inhibited tumor cell metastasis in a lung metastasis model. Thus, this study provided the first evidence that 14-3-3θ is a novel tumor suppressor and may serve as a candidate prognostic biomarker and target for new therapies in metastatic breast cancer.


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