Abstract
BackgroundSNAT1 is a subtype of the amino acid transport system A that has been implicated to play a potential role in cancer development and progression, yet its role in breast cancer remains unclear. In present study, we detected SNAT1 expression in breast cancers and explored its underlying mechanism in promoting breast carcinogenesis.MethodsRT-PCR and Western blotting were performed to analyze the transcription and protein levels of SNAT1 in breast cancer cell lines and fresh tissues. Tissue microarray blocks containing breast cancer specimens obtained from 210 patients were constructed. Expression of SNAT1 in these specimens was analyzed using immunohistochemical studies. SNAT1 was down-regulated by SNAT1-shRNA in breast cancer cells and the functional significance was measured.ResultsSNAT1 was up-regulated in breast cancer cell lines and breast cancer tissues. Overexpression of SNAT1 was observed in 127 cases (60.5%). Expression of SNAT1 was significantly associated with tumor size, nodal metastasis, advanced disease stage, Ki-67, and ER status. Suppression of endogenous SNAT1 leads to cell growth inhibition, cell cycle arrest, and apoptosis of 4T1 cells and lowered the phosphorylation level of Akt. SNAT1 expression correlated significantly with p-Akt expression in human breast cancer samples.ConclusionsThe cross-talk between Akt signaling and SNAT1 might play a critical role in the development and progression of breast cancer, providing an important molecular basis for novel diagnostic markers and new attractive targets in the treatment of breast cancer patients.
Highlights
SNAT1 is a subtype of the amino acid transport system A that has been implicated to play a potential role in cancer development and progression, yet its role in breast cancer remains unclear
SNAT1 expression in patients with breast cancer To analyze the expression pattern of SNAT1 in breast cancer, we firstly examined its mRNA and protein levels in breast cancer cell lines and breast cancer specimens and matched non-tumor tissues
In this study, we found that up-regulation of SNAT1 was significantly associated with (1) tumor size, lymph node metastasis and advanced disease stage, the most important clinical determinants of treatment and prognosis for breast cancer; (2) Ki-67 overexpression and negative ER expression, the most important biomarker guiding treatment and outcome for breast cancer; (3) elevated activity of Akt, determined by the expression of phosphorylated Akt (p-Akt)
Summary
SNAT1 is a subtype of the amino acid transport system A that has been implicated to play a potential role in cancer development and progression, yet its role in breast cancer remains unclear. Progress in treatment strategies and advances in our understanding of the molecular mechanisms of breast cancer, therapeutic effect increases and patients have longer survival duration. Several oncogenic kinase signaling pathways have been considered as potential targets for cancer treatment Among these pathways, PI3K/Akt/mTOR signaling has been shown to regulate cell proliferation, growth, migration and energy metabolism [3,4,5]. L-type amino acid transporter 1 (LAT1), for example, was widely investigated in various human solid tumors and increased expression of LAT1 was shown to be associated with tumor size, advanced disease stages, and Ki-67 labeling index and with poor patient outcome [8,9,10]. Given the importance of Akt pathway and amino acid transporters in nutrients and energy metabolism of tumor cells, we hypothesized that Akt activation might be associated with up-regulation of amino acid transporters [11]
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