丙氨酸-丝氨酸-半胱氨酸转运体2对肝细胞肝癌增殖和侵袭的影响

doi:10.52396/JUST-2021-0033

中国科学技术大学学报 ›› 2021, Vol. 51 ›› Issue (2): 129-139.DOI: 10.52396/JUST-2021-0033

• 研究论文:生命科学与医学 • 上一篇下一篇

丙氨酸-丝氨酸-半胱氨酸转运体2对肝细胞肝癌增殖和侵袭的影响

于淑琦¹, 张诗童¹, 王德政¹, 孙漪¹, 程美玲¹, 阚晨^1*, 倪芳^1,2,3*

1.安徽医科大学基础医学院病理生理学教研室,安徽合肥 230032;
2.中国科学技术大学附属第一医院(安徽省立医院)血液科,安徽合肥 230001;
3.中国科学技术大学生命科学与医学部基础医学院,安徽合肥 230027

收稿日期:2021-01-28 修回日期:2021-02-20 出版日期:2021-02-28 发布日期:2021-11-18
通讯作者: * E-mail:ckanahmu@163.com; fangni@ustc.edu.cn

Effects of alanine-serine-cysteine transporter 2 on proliferation and invasion of hepatocellular carcinoma

Yu Shuqi¹, Zhang Shitong¹, Wang Dezheng¹, Sun Yi ¹, Cheng Meiling¹,Kan Chen^1*, Ni Fang^1,2,3*

1. Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, Hefei 230032, China;
2. Department of Hematology, The First Affiliated Hospital of USTC(Anhui Provincial Hospital), Hefei 230001, China;
3. School of Basic Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China

Received:2021-01-28 Revised:2021-02-20 Online:2021-02-28 Published:2021-11-18
Contact: * E-mail: ckanahmu@163.com; fangni@ustc.edu.cn

摘要/Abstract

摘要： 代谢重编程是肿瘤的主要特征,肿瘤细胞通过上调丙氨酸-丝氨酸-半胱氨酸转运体2(ASCT2)来适应其对谷氨酰胺的需求.本研究发现肝细胞肝癌(HCC)组织中ASCT2的表达明显高于正常肝组织,并且,高表达ASCT2的患者长期生存率较低.在体外实验中,敲低ASCT2能显著抑制HCC细胞的增殖、克隆形成、迁移和侵袭.细胞周期分析表明,敲低ASCT2抑制了HCC细胞S期的比例.裸鼠成瘤实验证实敲低HCC细胞中的ASCT2能显著抑制肿瘤的生长.进一步的研究显示,敲低ASCT2可显著抑制HCC细胞线粒体氧化磷酸化(OXPHOS)、ATP生成以及AKT/S6通路的磷酸化水平.本研究结果表明,敲低ASCT2可抑制HCC细胞的恶性行为.此外,ASCT2下调后的HCC细胞线粒体代谢以及AKT/S6通路的磷酸化水平也受到抑制,提示线粒体代谢失调以及AKT/S6通路的异常活化与HCC的进展密切相关.

关键词: ASCT2, 肝细胞肝癌, 增殖, 侵袭, 代谢

Abstract: Metabolic reprogramming is a major feature of tumors, and tumor cells adapt to their glutamine needs by up-regulating the alanine-serine-cysteine transporter 2(ASCT2). It was found that the ASCT2 expression in hepatocellular carcinoma (HCC) tissues was significantly higher than that in normal liver tissues. In addition, the higher expression of ASCT2 in HCC patients was closely associated with poor survival.The knockdown of ASCT2 inhibited the proliferation, clone formation, migration and invasion of HCC cells in vitro.Cell cycle analysis suggested that knockdown of ASCT2 inhibited the proportion of HCC cells in the S phase. In vivo tumorigenic assay confirmed that the knockdown of ASCT2 in HCC cells could significantly inhibit tumor growth.Further studies showed that the knockdown of ASCT2 significantly reduced mitochondrial oxidative phosphorylation(OXPHOS),ATP production,and the phosphorylation level of AKT/S6 in HCC cells.Overall, our results showed that knockdown of ASCT2 could inhibit the malignancy of HCC cells. In addition, the mitochondrial metabolism and phosphorylation level of the AKT/S6 signaling pathway of HCC cells were also inhibited following the ASCT2 inhibition, suggesting that the dysregulated mitochondrial metabolism and abnormal activation of AKT/S6 signaling pathway were closely associated with the HCC progression.

Key words: ASCT2, hepatocellular carcinoma, proliferation, invasion, metabolism

中图分类号:

于淑琦, 张诗童, 王德政, 孙漪, 程美玲, 阚晨, 倪芳. 丙氨酸-丝氨酸-半胱氨酸转运体2对肝细胞肝癌增殖和侵袭的影响[J]. 中国科学技术大学学报, 2021, 51(2): 129-139.

YU Shuqi, ZHANG Shitong, WANG Dezheng, SUN Yi , CHENG Meiling, KAN Chen, NI Fang. Effects of alanine-serine-cysteine transporter 2 on proliferation and invasion of hepatocellular carcinoma[J]. Journal of University of Science and Technology of China, 2021, 51(2): 129-139.

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丙氨酸-丝氨酸-半胱氨酸转运体2对肝细胞肝癌增殖和侵袭的影响

Effects of alanine-serine-cysteine transporter 2 on proliferation and invasion of hepatocellular carcinoma

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