-
摘要:
SLC3A2（solute carrier family 3 member 2）是来自SLC3家族的一种Ⅱ型跨膜糖蛋白，是氨基酸转运体（heteromericamino acid transports, HATs）的重链组成部分。HATs在细胞中广泛表达并介导了几乎所有必需氨基酸的跨膜转运，保证细胞内氨基酸水平的稳定，对维持细胞正常的生物学功能具有重要作用。越来越多的研究报道，SLC3A2在多种肿瘤中高表达并参与细胞的恶性转化，然而其具体作用机制仅有初步报道尚未阐明。现就SLC3A2的结构、功能及其在肿瘤发生发展过程中的作用机制等综述如下。
Abstract:Solute carrier family 3 member 2 (SLC3A2) is a member of type Ⅱ transmembrane glycoprotein of the SLC3 family and a component of heteromericamino acid transports (HATs). While widely expressed in cells, HATs mediate the transmembrane transport of all essential amino acids and maintain the intracellular stability of amino acid concentrations, which is important to the normal function of cells. Researches show that SLC3A2 is highly expressed in various tumor cells and involved in the malignant transformation of cells.However, the mechanisms are still lacking. In this review, we will discuss the advances in the structure and function of SLC3A2 and its mechanism in tumor occurrence and development.
-
-
![]()
图 1 CD98hc (SLC3A2) 的结构及其与SLC7家族成员、整合素相结合的示意图
Figure 1 Schematic illustration of SLC3A2 and its interactions with SLC7 families and integrins
-
[1] Zhang WC, Shyh-Chang N, Yang H, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis[J]. Cell, 2012, 148(1-2): 259-72. doi: 10.1016/j.cell.2011.11.050
[2] Kim D, Fiske BP, Birsoy K, et al. SHMT2 drives glioma cell surviva1 in ischaemia but imposes a dependence on glycine clearance[J]. Nature, 2015, 520(7547): 363-7. doi: 10.1038/nature14363
[3] Hensley CT, Wasti AT, DeBerardinis RJ. Glutamine and cancer: cell biology, physiology, and clinical opportunities[J]. J Clin Invest, 2013, 123(9): 3678-84. doi: 10.1172/JCI69600
[4] Daye D, Wellen KE. Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis[J]. Semin Cell Dev Biol, 2012, 23(4): 362-9. doi: 10.1016/j.semcdb.2012.02.002
[5] de la Ballina LR, Cano-Crespo S, González-Muñoz E, et al. Amino Acid Transport Associated to Cluster of Differentiation 98 Heavy Chain (CD98hc) Is at the Cross-road of Oxidative Stress and Amino Acid Availability[J]. J Biol Chem, 2016, 291(18): 9700-11. doi: 10.1074/jbc.M115.704254
[6] Fort J, de la Ballina LR, Burghardt HE, et al. The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane[J]. J Biol Chem, 2007, 282(43): 31444-52. doi: 10.1074/jbc.M704524200
[7] Haynes BF. Human T lymphocyte antigens as defined by monoclonal antibodies[J]. Immunol Rev, 1981, 57: 127-61. doi: 10.1111/imr.1981.57.issue-1
[8] Feral CC, Nishiya N, Fenczik CA, et al. CD98hc (SLC3A2) mediates integrin signaling[J]. Proc Natl Acad Sci U S A, 2005, 102(2): 355-60. doi: 10.1073/pnas.0404852102
[9] Fenczik CA, Zent R, Dellos M, et al. Distinct domains of CD98hc regulateintegrins and amino acid transport[J]. J Biol Chem, 2001, 276(12): 8746-52. doi: 10.1074/jbc.M011239200
[10] Cantor JM, Ginsberg MH. CD98 at the crossroads of adaptive immunity and cancer[J]. J Cell Sci, 2012, 125(Pt 6): 1373-82.
[11] Verrey F, Closs EI, Wagner CA, et al. CATs and HATs: the SLC7 family of amino acid transporters[J]. Pflugers Arch, 2004, 447(5): 532-42. doi: 10.1007/s00424-003-1086-z
[12] Meier C, Ristic Z, Klauser S, et al. Activation of system L heterodimeric amino acid exchangers by intracellular substrates[J]. EMBO J, 2002, 21(4): 580-9. doi: 10.1093/emboj/21.4.580
[13] Kinne A, Schülein R, Krause G. Primary and secondary thyroid hormone transporters[J]. Thyroid Res, 2011, 4 Suppl 1: S7. https://www.researchgate.net/profile/Anita_Kinne/publication/51565138_Primary_and_secondary_thyroid_hormone_transporters/links/0c96052740b5b07e7e000000.pdf?inViewer=true&pdfJsDownload=true&disableCoverPage=true&origin=publication_detail
[14] Kanai Y, Fukasawa Y, Cha SH, et al. Transport properties of a system y+L neutral and basic amino acid transporter. Insights into the mechanisms of substrate recognition[J]. J Biol Chem, 2000, 275(27): 20787-93. doi: 10.1074/jbc.M000634200
[15] Bridges RJ, Natale NR, Patel SA. System xc cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS[J]. Br J Pharmacol, 2012, 165(1): 20-34. doi: 10.1111/j.1476-5381.2011.01480.x
[16] Fukasawa Y, Segawa H, Kim JY, et al. Identification and characterization of a Na (+)-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral D-and L-amino acids[J]. J Biol Chem, 2000, 275(13): 9690-8. doi: 10.1074/jbc.275.13.9690
[17] Kabir-Salmani M, Fukuda MN, Kanai-Azuma M, et al. The membrane-spanning domain of CD98 heavy chain promotes alpha (v) beta3 integrinsignals in human extravilloustrophoblasts[J]. Mol Endocrinol, 2008, 22(3): 707-15. doi: 10.1210/me.2007-0243
[18] Poettler M, Unseld M, Braemswig K, et al. CD98hc (SLC3A2) drives integrin-dependent renal cancer cell behavior[J]. Mol Cancer, 2013, 12:169. doi: 10.1186/1476-4598-12-169
[19] Hara K, Kudoh H, Enomoto T, et al. Malignant transformation of NIH3T3 cells by overexpression of early lymphocyte activation antigen CD98[J]. Biochem Biophys Res Commun, 1999, 262(3): 720-5. doi: 10.1006/bbrc.1999.1051
[20] Shishido T, Uno S, Kamohara M, et al. Transformation of BALB3T3 cells caused by over-expression of rat CD98 heavy chain (HC) requires its association with light chain: mis-sense mutation in a cysteine residue of CD98HC eliminates its transforming activity[J]. Int J Cancer, 2000, 87(3): 311-6. doi: 10.1002/(ISSN)1097-0215
[21] Estrach S, Lee SA, Boulter E, et al. CD98hc (SLC3A2) loss protects against ras-driven tumorigenesis by modulating integrin-mediated mechanotransduction[J]. Cancer Res, 2014, 74(23): 6878-89. doi: 10.1158/0008-5472.CAN-14-0579
[22] Nguyen HT, Dalmasso G, Torkvist L, et al. CD98 expression modulates intestinal homeostasis, inflammation, and colitis-associated cancer in mice[J]. J Clin Invest, 2011, 121(5): 1733-47. doi: 10.1172/JCI44631
[23] Nguyen HT, Dalmasso G, Yan Y, et al. Intestinal epithelial cell-specific CD98 expression regulates tumorigenesis in Apc (Min/+) mice[J]. Lab Invest, 2012, 92(8): 1203-12. doi: 10.1038/labinvest.2012.83
[24] Kaira K, Ohde Y, Endo M, et al. Expression of 4F2hc (CD98) in pulmonary neuroendocrine tumors[J]. Oncol Rep, 2011, 26(4): 931-7.
[25] Furuya M, Horiguchi J, Nakajima H, et al. Correlation of L-type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis[J]. Cancer Sci, 2012, 103(2): 382-9. doi: 10.1111/cas.2012.103.issue-2
[26] Kaira K, Takahashi T, Abe M, et al. CD98 expression is associated with the grade of malignancy in thymic epithelial tumors[J]. Oncol Rep, 2010, 24(4): 861-7. https://www.researchgate.net/publication/46111383_CD98_expression_is_associated_with_the_grade_of_malignancy_in_thymic_epithelial_tumors
[27] Santiago-Gómez A, Barrasa JI, Olmo N, et al. 4F2hc-silencing impairs tumorigenicity of HeLa cells via modulation of galectin-3 and β-catenin signaling, and MMP-2 expression[J]. Biochim Biophys Acta, 2013, 1833(9): 2045-56. doi: 10.1016/j.bbamcr.2013.04.017
[28] Nicklin P, Bergman P, Zhang B, et al. Bidirectional transport of amino acids regulates mTOR and autophagy[J]. Cell, 2009, 136(3): 521-34. doi: 10.1016/j.cell.2008.11.044
[29] Kurayama R, Ito N, Nishibori Y, et al. Role of amino acid transporter LAT2 in the activation of mTORC1 pathway and the pathogenesis of crescentic glomerulonephritis[J]. Lab Invest, 2011, 91(7): 992-1006. doi: 10.1038/labinvest.2011.43
[30] Caudroy S, Polette M, Nawrocki-Raby B, et al. EMMPRIN-mediated MMP regulation in tumor and endothelial cells[J]. Clin Exp Metastasis, 2002, 19(8): 697-702. doi: 10.1023/A:1021350718226
[31] Fogelstrand P, Féral CC, Zargham R, et al. Dependence of proliferative vascular smooth muscle cells on CD98hc (4F2hc, SLC3A2)[J]. J Exp Med, 2009, 206(11): 2397-406. doi: 10.1084/jem.20082845
[32] Oda K, Hosoda N, Endo H, et al. L-type amino acid transporter 1 inhibitors inhibit tumor cell growth[J]. Cancer Sci, 2010, 101(1): 173-9. doi: 10.1111/cas.2009.101.issue-1
[33] Yun DW, Lee SA, Park MG, et al. JPH203, an L-type amino acid transporter 1-selective compound, induces apoptosis of YD-38 human oral cancer cells[J]. J Pharmacol Sci, 2014, 124(2): 208-17. doi: 10.1254/jphs.13154FP
-
期刊类型引用(7)
1. 秦浩然，朱红. 胰腺癌术后帕博利珠单抗免疫治疗联合化疗对预后的影响. 现代医学与健康研究电子杂志. 2023(08): 80-82 . 
百度学术
2. 罗旭，党会芬，王千千，王玉凤，田迎霞. 免疫、靶向及节拍化疗综合治疗晚期胰腺癌1例. 甘肃医药. 2023(04): 376-378+381 . 百度学术
3. 段伯焘，赵学凯，高倩倩，逯永晋，周磊. 2020年版与2018年版中国胰腺癌综合诊治指南比较分析. 中国普通外科杂志. 2022(03): 287-294 . 百度学术
4. 李政晓，薛彩强，赵君. 影像组学在肿瘤微环境评估中的研究进展. 兰州大学学报(医学版). 2022(08): 76-79 . 百度学术
5. 雷洋洋，王小林. “精准医学”模式下胰腺癌防治的探索与进展. 复旦学报(医学版). 2021(02): 255-260 . 百度学术
6. 董静，牛昆，庞丽然，江一帆. 免疫治疗相关单克隆抗体靶点在三阴性乳腺癌中的研究现状. 现代肿瘤医学. 2021(22): 4044-4049 . 百度学术
7. 任刚，夏廷毅，王颖杰. 如何发挥放疗在胰腺癌治疗中的作用. 肿瘤防治研究. 2021(11): 989-993 . 本站查看
其他类型引用(7)
下载:
计量
- 文章访问数: 2965
- HTML全文浏览量: 541
- PDF下载量: 2051
- 被引次数: 14
