Oncotarget

Research Papers:

Increased SNAT1 is a marker of human osteosarcoma and potential therapeutic target

Miaomiao Wang, Ying Liu, Wenzheng Fang, Ke Liu, Xiaodong Jiao, Zhan Wang, Jiejun Wang _ and Yuan-Sheng Zang

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Oncotarget. 2017; 8:78930-78939. https://doi.org/10.18632/oncotarget.20693

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Abstract

Miaomiao Wang1, Ying Liu1, Wenzheng Fang1, Ke Liu1, Xiaodong Jiao1, Zhan Wang1, Jiejun Wang1 and Yuan-Sheng Zang1

1Department of Medical Oncology, Changzheng Hospital, Shanghai 200070, China

Correspondence to:

Jiejun Wang, email: jiejunw@csco.org.cn

Yuan-Sheng Zang, email: doctorzangys@163.com

Keywords: SNAT1, osteosarcoma, prognosis, metastasis, MMP9

Abbreviations: OS: Osteosarcoma

Received: March 10, 2017     Accepted: May 22, 2017     Published: September 05, 2017

ABSTRACT

Background: SLC38A1/SNAT1 has been found to play an essential role in human development, but its role in osteosarcoma (OS) has yet to be evaluated. The purpose of this study was to assess the expression of SLC38A1/SNAT1 in patients with OS, and further investigate the mechanisms by which it affects tumor growth and metastasis.

Methods: Tissue microarray blocks and immunohistochemical studies were carried out to assess the expression of SNAT1 in 165 OS specimens. Its correlation with clinicopathological characteristics was then analyzed. The function of SNAT1 in OS cells was investigated by silencing SNAT1 using SNAT1-shRNA in vitro and in vivo.

Results: SNAT1 was highly expressed in 85% OS and significantly closely associated with pulmonary metastasis. Patients with high SNAT1 expression survived for shorter periods than those with low SNAT1 expression. Suppression of endogenous SNAT1 led to inhibition of cell proliferation, cell colony formation, and cell migration in vitro, and retarded tumor growth in xenograft models. Silencing SNAT1 reduced expression of MMP9, vimentin, fibronectin, p-Akt, p-mTOR, and VEGF.

Conclusions: Our results indicated that increased expression of SNAT1 is a common event in OS. SNAT1 played an essential role in the development and progression of osteosarcoma, which may serve as a prognostic and therapeutic marker of OS.


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