GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5 enhancement of tumor growth and metastasis
GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5 enhancement of tumor growth and metastasis
复制标题
GSE1通过SLC7A5增强肿瘤生长和转移来预测胃癌患者的不良生存结果
DOI：
10.1074/jbc.ra117.001103
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发表时间：
2018-03-16
影响因子：
4.8
通讯作者：
Wu, Zhengsheng
中科院分区：
文献类型：
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作者：
Ding, Keshuo;Tan, Sheng;Wu, Zhengsheng
胃癌仍然是一种预后不良的恶性肿瘤。在此我们报道，GSE1这种富含脯氨酸的蛋白质在人类胃癌进展中具有作用。观察到GSE1在人类胃癌组织中的表达比正常胃组织高得多，并且GSE1的表达与胃癌患者的淋巴结转移、组织学分级、浸润深度和临床分期呈正相关。此外，GSE1的表达还与队列中术后无复发生存期和总生存期的降低有关。在胃癌细胞系中强制表达GSE1导致细胞增殖增加、集落形成增多、细胞迁移和侵袭能力增强。进一步地，在异种移植模型中，强制表达GSE1还增加了肿瘤大小并增强了肺转移。用shRNAs敲低内源性GSE1在体外和体内都降低了胃癌细胞的致癌性和侵袭性。此外，GSE1被确定为miR - 200b和miR - 200c的直接靶标。而且，GSE1正向调控下游基因SLC7A5（也称为LAT - 1），这是通过mRNA测序扫描并验证的。因此，GSE1在人类胃癌中具有致癌作用，针对胃癌中抑制GSE1功能的靶向治疗方法值得进一步考虑。
Gastric cancer remains a malignancy with poor survival outcome. We herein report that GSE1, a proline-rich protein, possesses a role in the progression of human gastric cancer. The expression of GSE1 was observed to be much higher in human gastric cancer tissues compared with normal gastric tissues, and GSE1 expression correlated positively with lymph node metastasis, histological grade, depth of invasion, and clinical stage in gastric cancer patients. Moreover, GSE1 expression was also associated with decreased post-operative relapse-free survival and overall survival in the cohort. The forced expression of GSE1 in gastric cancer cell lines resulted in increased cell proliferation, increased colony formation, enhanced cell migration, and invasion. Furthermore, forced expression of GSE1 also increased tumor size and enhanced lung metastasis in xenograft models. The depletion of endogenous GSE1 with shRNAs decreased the oncogenicity and invasiveness of gastric cancer cells both in vitro and in vivo. In addition, GSE1 was determined to be a direct target of miR-200b and miR-200c. Furthermore, GSE1 positively regulated the downstream gene SLC7A5 (also known as LAT-1), which was scanned and verified from mRNA sequencing. GSE1 therefore possesses an oncogenic role in human gastric cancer, and targeted therapeutic approaches to inhibit GSE1 function in gastric cancer warrant further consideration.