Summary
Current studies have demonstrated that SLC38A1 proteins play a causal role in neoplastic cell transformation. The twofold aim of this study was to provide insight into whether a variance in the expression of SLC38A1 exists between human colorectal cancer and healthy human tissues and to determine how silencing or overexpressing the SLC38A1 gene could affect the proliferation, viability and migration of colorectal cancer cells. Immunohistochemical staining was used to analyze the expression of SLC38A1 in colorectal cancer tissues and adjacent normal mucosa in 77 patients who underwent surgical resection. The expression of SLC38A1 in colorectal cancer tissues and cell lines was detected using RT-PCR and Western blotting. Two colorectal cancer cell lines SW480 and HCT116 were used to examine whether silencing SLC38A1 with siRNA and overexpressing SLC38A1 with shRNA could affect cell viability and migration. As a result, the SLC38A1 protein was very low or undetectable in the normal colon mucosa. In contrast, strong staining of SLC38A1 protein was found in the cytoplasm in 79.2% colorectal cancer samples. More pronounced SLC38A1 expression in colorectal cancer tissues was significantly associated with tumor node metastasis (TNM) stage. Inhibition of SLC38A1 reduced tumour growth and suppressed proliferation and migration of SW480 cells. In contrast, overexpression of SLC38A1 had the opposite effects on HCT116 cells. SLC38A1 is overexpressed in colorectal cancer, which suggests that it is associated with tumour progression. These results encourage the exploration of SLC38A1 as a target for intervention in colorectal cancer.
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Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 2010,127(12): 2893–2917
Kobayashi H, Mochizuki H, Sugihara K, et al. Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery, 2007,141(1): 67–75
Fang J, Mao D, Smith CH, et al. IGF regulation of neutral amino acid transport in the BeWo choriocarcinoma cell line (b30 clone): evidence for MAP kinase-dependent and MAP kinase-independent mechanisms. Growth Horm IGF Res, 2006,16(5-6):318–325
Xie J, Chen Z, Liu L, et al. shRNA-mediated slc38a1 silencing inhibits migration, but not invasiveness of human pancreatic cancer cells. Chin J Cancer Res, 2013,25(5): 514–519
Wang K, Cao F, Fang W, et al. Activation of SNAT1/SLC38A1 in human breast cancer: correlation with p-Akt overexpression. BMC Cancer, 2013,13:343
Yu WL, Cong WM, Zhang Y, et al. Overexpression of ATA1/SLC38A1 predicts future recurrence and death in Chinese patients with hilar cholangiocarcinoma. J Surg Res, 2011,171(2): 663–668
Yu G, Wang J, Chen Y, et al. Tissue microarray analysis reveals strong clinical evidence for a close association between loss of annexin A1 expression and nodal metastasis in gastric cancer. Clin Exp Metastasis, 2008,25(7): 695–702
McGivan JD, Bungard CI. The transport of glutamine into mammalian cells. Front Biosci, 2007,12: 874–882
Solbu TT, Bjørkmo M, Berghuis P, et al. SAT1, a glutamine transporter, is preferentially expressed in GABAergic neurons. Front Neuroanat, 2010,4:1
Albers A, Bröer A, Wagner CA, et al. Na+ transport by the neural glutamine transporter ATA1. Pflugers Arch, 2001,443(1): 92–101
Kondoh N, Imazeki N, Arai M, et al. Activation of a system A amino acid transporter, ATA1/SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues. Int J Oncol, 2007,31(1): 81–87
Ogura M, Takarada T, Nakamichi N, et al. Exacerbated vulnerability to oxidative stress in astrocytic C6 glioma cells with stable overepression of glutamine transporter slc38a1. Neurochem Int, 2011,58(4): 504–511
Xie J, Li P, Gao H, et al. Overexpression of SLC38A1 is associated with poorer prognosis in Chinese patients with gastric cancer. BMC Gastroenterology, 2014,14:70
Varoqui H, Zhu H, Yao D, et al. Cloning and functional identification of a neuronal glutamine transporter. J Biol Chem, 2007,275(6): 4049–1054
Medina MA, Sánchez-Jiménez F, Márquez J, et al. Relevance of glutamine metabolism to tumor cell growth. Mol Cell Biochem, 1992,113(1): 1–15
Chen MK, Espat NJ, Bland KI, et al. Influence of progressive tumor growth on glutamine metabolism in skeletal muscle and kidney. Ann Surg, 1993,217(6): 655–666
Xu S, Tang K, Meng L, et al. Suppression of amino acid transporter LAT3 expression on proliferation of K562 cells. J Huazhong Uni Sci Technol Med Sci, 2013,33(5): 632–635
Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditid elegans. Nature, 1998,391(6669): 806–811
Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediated RNA interference in cultured mammalian cells. Nature, 2001,411(6836): 494–498
Chakraborty C. Potentiality of small interfering RNAs (siRNA) as recent therapeutic targets for gene-silencing. Curr Drug Targets, 2007,8(3): 469–482
Rubinson DA, Dillon CP, Kwiatkowski AV, et al. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nature Genetics, 2003,33(3): 401–406
Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science, 2002,296(5567): 550–553
Rosario FJ, Jansson N, Kanai Y, et al. Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters. Endocrinology, 2011,152(3): 1119–1129
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We are grateful to the laboratory staff in the Department of Urology, Zhongnan Hospital of Wuhan University for their help.
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The authors contributed equally to this work.
This project was supported in part by grants from National Natural Science Foundation of China (No. 81072152), Research Foundation of Health and Family Planning Commission of Hubei Province (No. WJ2015MA010), Natural Science Foundation of Hubei Province (No. 2015CFA027) and Clinical Medical Research Center of Peritoneal Cancer of Wuhan (No. 2015060911020462).
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Zhou, Ff., Xie, W., Chen, Sq. et al. SLC38A1 promotes proliferation and migration of human colorectal cancer cells. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 37, 30–36 (2017). https://doi.org/10.1007/s11596-017-1690-3
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DOI: https://doi.org/10.1007/s11596-017-1690-3