Abstract
BackgroundCurrent literature has demonstrated that host glutamine depletion facilitates tumorigenesis. Likewise, the glutamine transporter SLC38A1 is putatively associated with malignant transformation and tumor progression. Taken together, this forms the premise for undertaking the current study. The twofold aim of this study was to provide insight into whether or not a variance in the expression of SLC38A1 exists between human gastric cancer and healthy human tissues, and to determine how silencing the SLC38A1 gene could affect the proliferation, viability, migration, and invasion of gastric cancer cells.MethodsImmunohistochemical staining was used to analyze the expression of SLC38A1 in gastric cancer tissues and adjacent healthy mucosa in 896 patients with pathologically confirmed gastric cancer who had underwent R0 resection. SH-10-TC cells (a gastric cancer cell line) were used to examine whether silencing SLC38A1 with siRNA could affect cell viability, migration and invasion.ResultsThe SLC38A1 protein was very low or undetectable in healthy gastric mucosa. In contrast, strong staining of SLC38A1 protein was found in the cytoplasm in 495 out of the 896 gastric cancer samples. More pronounced SLC38A1 expression in gastric cancer tissues was significantly associated with age, differentiation status, lymph node metastasis, TNM stage and PCNA (proliferating cell nuclear antigen) expression. Upon univariate survival analysis, SLC38A1 expression was correlated with poor survival. Multivariate survival analysis revealed that SLC38A1 was an independent prognostic factor.ConclusionSLC38A1 is overexpressed in gastric cancer, which suggests that it is contributory to tumor progression. These results encourage the exploration of SLC38A1 as a target for intervention in gastric cancer.
Highlights
Current literature has demonstrated that host glutamine depletion facilitates tumorigenesis
Solute carrier family 38 (SLC38A1) expression and clinicopathologic factors SLC38A1 overexpression was closely associated with old age (>60 yrs), differentiation status, regional lymph node metastasis, TNM stage (III), and positive Proliferating cell nuclear antigen (PCNA) expression (Table 1), but not with gender, tumor size, tumor location, operation manner, lymphovascular invasion, depth of tumor invasion, and p53 expression
Prognostic factors of overall survival SLC38A1 expression in cancer tissue was associated with poorer prognosis
Summary
Current literature has demonstrated that host glutamine depletion facilitates tumorigenesis. The glutamine transporter SLC38A1 is putatively associated with malignant transformation and tumor progression. Taken together, this forms the premise for undertaking the current study. Amino acid transporters are essential for a variety of physiological cellular processes, including uptake of nutrients, energy and chemical metabolism, as well as malignant transformation [1]. Among the various amino acid transporters, system L-type amino acid transporter-1 (LAT-1) is up-regulated in a wide variety of human cancers, including esophageal adenocarcinoma [2], oral squamous cell carcinoma [3], colorectal adenocarcinoma [4], and liver cancer [5]. System A is a Na+-dependent active transport system, known to mediate the uptake of amino acids with small side chains (e.g., alanine, serine, proline and glutamine) [1]. Its activity is highly influenced by pH, cell volume, and a variety of hormones, such as insulin, glucagon, and insulin-like growth factor-I [1]
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