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SLC1A5上调促进结直肠癌细胞生长和存活。

Upregulated SLC1A5 promotes cell growth and survival in colorectal cancer.

作者信息

Huang Fang, Zhao Yingchao, Zhao Junzhang, Wu Shuang, Jiang Yao, Ma Hong, Zhang Tao

机构信息

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, Hubei, China.

出版信息

Int J Clin Exp Pathol. 2014 Aug 15;7(9):6006-14. eCollection 2014.

Abstract

Glutamine metabolism is essential for tumorigenesis of colorectal cancer, cancer cells remodel their glutamine metabolic pathways to fuel rapid proliferation. SLC1A5 is an important transporter of glutamine various cancer cells. In this study, we investigated SLC1A5 protein expression in colorectal cancer and evaluated its clinical significance and functional importance. Immunohistochemical analysis was performed on tissue microarrays containing 90 pairs of cancer and adjacent normal tissues from colorectal cancer patients, we found that SLC1A5 expression increased significantly in colorectal cancer compared with normal mucosa tissues (P < 0.001). We further validated SLC1A5 overexpression in 12 pairs of fresh cancer and adjacent normal mucosa tissues from colorectal cancer patients by Western blot (P < 0.05). SLC1A5 expression levels were strongly associated with T stage of tumor (P < 0.05), and the tubular adenocarcinoma subtype (P < 0.001). Moreover, downregulation of SLC1A5 by synthetic siRNA could suppress proliferation and induce apoptosis in colorectal cancer cell lines HT29 and HCT116. In conclusion, our results provide for the first time the differential expression in human colorectal cancer and normal tissues, and a functional link between SLC1A5 expression and growth and survival of colorectal cancer, making it an attractive target in colorectal cancer treatment.

摘要

谷氨酰胺代谢对结直肠癌的肿瘤发生至关重要,癌细胞重塑其谷氨酰胺代谢途径以支持快速增殖。SLC1A5是多种癌细胞中谷氨酰胺的重要转运体。在本研究中,我们调查了结直肠癌中SLC1A5蛋白的表达情况,并评估了其临床意义和功能重要性。对包含90对来自结直肠癌患者的癌组织和相邻正常组织的组织芯片进行免疫组化分析,我们发现与正常黏膜组织相比,结直肠癌中SLC1A5的表达显著增加(P < 0.001)。我们通过蛋白质印迹法进一步验证了12对来自结直肠癌患者的新鲜癌组织和相邻正常黏膜组织中SLC1A5的过表达(P < 0.05)。SLC1A5的表达水平与肿瘤的T分期(P < 0.05)以及管状腺癌亚型(P < 0.001)密切相关。此外,通过合成的小干扰RNA下调SLC1A5可抑制结直肠癌细胞系HT29和HCT116的增殖并诱导其凋亡。总之,我们的结果首次揭示了人结直肠癌组织与正常组织中的差异表达,以及SLC1A5表达与结直肠癌生长和存活之间的功能联系,使其成为结直肠癌治疗中一个有吸引力的靶点。

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