Research progress of solute carriers related genes in malignant tumors

doi:10.3760/cma.j.cn371439-20230305-00056

Abstract

Abstract:

As a transport channel for amino acids， solute carrier （SLC） exists in all kinds of cells， and its function is to transport various amino acids and provide necessary nutrients for the growth and development of cells. In recent years， SLC7A5 and SLC7A11 genes of SLC7 family members have been found to be highly expressed in various malignant tumors， which can promote the occurrence and development of tumors by providing necessary amino acids for tumors. Studies have shown that these genes are associated with a variety of malignant tumors， and their expression is closely related to the growth， metastasis， treatment and prognosis of tumor cells. Moreover， the results of multiple studies suggest that SLC7A5 and SLC7A11 genes can be used as therapeutic targets for malignant tumors. Clarifying the expression and clinical significance of the above genes in malignant tumors， the molecular biological mechanism and the progress of molecular targeted therapy are helpful to provide a new way for the diagnosis and treatment of malignant tumors.

Key words: Solute carrier proteins, Neoplasms, Gene expression, Molecular biology, Molecular targeted therapy

Liu Bohan, Huang Junxing. Research progress of solute carriers related genes in malignant tumors[J]. Journal of International Oncology, 2023, 50(5): 280-284.

References 35

[1]	Fairweather SJ, Shah N, Bröer S. Heteromeric solute carriers: function, structure, pathology and pharmacology[J]. Adv Exp Med Biol, 2021, 21: 13-127. DOI: 10.1007/5584_2020_584. doi: 10.1007/5584_2020_584 pmid: 33052588
[2]	汤志全, 石丽, 熊晶. 溶质载体SLC家族在非酒精性脂肪性肝病中的研究进展[J]. 遗传, 2022, 44(10): 881-898. DOI: 10.16288/j.yczz.22-238. doi: 10.16288/j.yczz.22-238
[3]	Lu X. The role of large neutral amino acid transporter (LAT1) in cancer[J]. Curr Cancer Drug Targets, 2019, 19(11): 863-876. DOI: 10.2174/1568009619666190802135714. doi: 10.2174/1568009619666190802135714 pmid: 31376820
[4]	Pizzagalli MD, Bensimon A, Superti-Furga G. A guide to plasma membrane solute carrier proteins[J]. FEBS J, 2021, 288(9): 2784-2835. DOI: 10.1111/febs.15531. doi: 10.1111/febs.15531
[5]	Scalise M, Scanga R, Console L, et al. Chemical approaches for studying the biology and pharmacology of membrane transporters: the histidine/large amino acid transporter SLC7A5 as a benchmark[J]. Molecules, 2021, 26(21): 6562. DOI: 10.3390/molecules26216562. doi: 10.3390/molecules26216562
[6]	Kanai Y. Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics[J]. Pharmacol Ther, 2022, 230: 107964. DOI: 10.1016/j.pharmthera.2021.107964. doi: 10.1016/j.pharmthera.2021.107964
[7]	Liu Y, Ma G, Liu J, et al. SLC7A5 is a lung adenocarcinoma-specific prognostic biomarker and participates in forming immunosuppressive tumor microenvironment[J]. Heliyon, 2022, 8(10): e10866. DOI: 10.1016/j.heliyon.2022.e10866. doi: 10.1016/j.heliyon.2022.e10866
[8]	Huang P, Xia L, Guo Q, et al. Genome-wide association studies identify miRNA-194 as a prognostic biomarker for gastrointestinal cancer by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5[J]. Front Oncol, 2022, 12: 1025594. DOI: 10.3389/fonc.2022.1025594. doi: 10.3389/fonc.2022.1025594
[9]	Najumudeen AK, Ceteci F, Fey SK, et al. The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer[J]. Nat Genet, 2021, 53(1): 16-26. DOI: 10.1038/s41588-020-00753-3. doi: 10.1038/s41588-020-00753-3 pmid: 33414552
[10]	Kurozumi S, Kaira K, Matsumoto H, et al. Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer[J]. Sci Rep, 2022, 12(1): 2742. DOI: 10.1038/s41598-022-06615-8. doi: 10.1038/s41598-022-06615-8 pmid: 35177712
[11]	Bodoor K, Almomani R, Alqudah M, et al. LAT1 (SLC7A5) overexpression in negative Her2 group of breast cancer: a potential therapy target[J]. Asian Pac J Cancer Prev, 2020, 21(5): 1453-1458. DOI: 10.31557/APJCP.2020.21.5.1453. doi: 10.31557/APJCP.2020.21.5.1453
[12]	Wang Q, Liu H, Liu Z, et al. Circ-SLC7A5, a potential prognostic circulating biomarker for detection of ESCC[J]. Cancer Genet, 2020, 240: 33-39. DOI: 10.1016/j.cancergen.2019.11.001. doi: 10.1016/j.cancergen.2019.11.001
[13]	Lin W, Wang C, Liu G, et al. SLC7A11/xCT in cancer: biological functions and therapeutic implications[J]. Am J Cancer Res, 2020, 10(10): 3106-3126. pmid: 33163260
[14]	Kim DH, Kim WD, Kim SK, et al. TGF-β1-mediated repression of SLC7A11 drives vulnerability to GPX4 inhibition in hepatocellular carcinoma cells[J]. Cell Death Dis, 2020, 11(5): 406. DOI: 10.1038/s41419-020-2618-6. doi: 10.1038/s41419-020-2618-6 pmid: 32471991
[15]	Feng L, Zhao K, Sun L, et al. SLC7A11 regulated by NRF2 modulates esophageal squamous cell carcinoma radiosensitivity by inhibiting ferroptosis[J]. J Transl Med, 2021, 19(1): 367. DOI: 10.1186/s12967-021-03042-7. doi: 10.1186/s12967-021-03042-7 pmid: 34446045
[16]	Hu K, Li K, Lv J, et al. Suppression of the SLC7A11/glutathione axis causes synthetic lethality in KRAS-mutant lung adenocarcinoma[J]. J Clin Invest, 2020, 130(4): 1752-1766. DOI: 10.1172/JCI124049. doi: 10.1172/JCI124049 pmid: 31874110
[17]	Chen MC, Hsu LL, Wang SF, et al. ROS mediate xCT-dependent cell death in human breast cancer cells under glucose deprivation[J]. Cells, 2020, 9(7): 1598. DOI: 10.3390/cells9071598. doi: 10.3390/cells9071598
[18]	Ruiu R, Rolih V, Bolli E, et al. Fighting breast cancer stem cells through the immune-targeting of the xCT cystine-glutamate antiporter[J]. Cancer Immunol Immunother, 2019, 68(1): 131-141. DOI: 10.1007/s00262-018-2185-1. doi: 10.1007/s00262-018-2185-1 pmid: 29947961
[19]	Badgley MA, Kremer DM, Maurer HC, et al. Cysteine depletion induces pancreatic tumor ferroptosis in mice[J]. Science, 2020, 368(6486): 85-89. DOI: 10.1126/science.aaw9872. doi: 10.1126/science.aaw9872 pmid: 32241947
[20]	Bröer S. Amino acid transporters as targets for cancer therapy: why, where, when, and how[J]. Int J Mol Sci, 2020, 21(17): 6156. DOI: 10.3390/ijms21176156. doi: 10.3390/ijms21176156
[21]	Wang Q, Holst J. L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia[J]. Am J Cancer Res, 2015, 5(4): 1281-1294. pmid: 26101697
[22]	Koppula P, Zhuang L, Gan B. Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy[J]. Protein Cell, 2021, 12(8): 599-620. DOI: 10.1007/s13238-020-00789-5. doi: 10.1007/s13238-020-00789-5
[23]	Quan L, Ohgaki R, Hara S, et al. Amino acid transporter LAT1 in tumor-associated vascular endothelium promotes angiogenesis by regulating cell proliferation and VEGF-A-dependent mTORC1 activation[J]. J Exp Clin Cancer Res, 2020, 39(1): 266. DOI: 10.1186/s13046-020-01762-0. doi: 10.1186/s13046-020-01762-0
[24]	Cormerais Y, Giuliano S, LeFloch R, et al. Genetic disruption of the multifunctional CD98/LAT1 complex demonstrates the key role of essential amino acid transport in the control of mTORC1 and tumor growth[J]. Cancer Res, 2016, 76(15): 4481-4492. DOI: 10.1158/0008-5472.CAN-15-3376. doi: 10.1158/0008-5472.CAN-15-3376 pmid: 27302165
[25]	Galan-Cobo A, Sitthideatphaiboon P, Qu X, et al. LKB1 and KEAP1/NRF2 pathways cooperatively promote metabolic reprogramming with enhanced glutamine dependence in KRAS-mutant lung adenocarcinoma[J]. Cancer Res, 2019, 79(13): 3251-3267. DOI: 10.1158/0008-5472.CAN-18-3527. doi: 10.1158/0008-5472.CAN-18-3527 pmid: 31040157
[26]	Liu X, Olszewski K, Zhang Y, et al. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer[J]. Nat Cell Biol, 2020, 22(4): 476-486. DOI: 10.1038/s41556-020-0496-x. doi: 10.1038/s41556-020-0496-x pmid: 32231310
[27]	Wu Z, Xu J, Liang C, et al. Emerging roles of the solute carrier family in pancreatic cancer[J]. Clin Transl Med, 2021, 11(3): e356. DOI: 10.1002/ctm2.356. doi: 10.1002/ctm2.356 pmid: 33783998
[28]	Häfliger P, Charles RP. The L-type amino acid transporter LAT1—an emerging target in cancer[J]. Int J Mol Sci, 2019, 20(10): 2428. DOI: 10.3390/ijms20102428. doi: 10.3390/ijms20102428
[29]	Maekawa-Matsuura M, Fujieda K, Maekawa Y, et al. LAT1-targeting thermoresponsive liposomes for effective cellular uptake by cancer cells[J]. ACS Omega, 2019, 4(4): 6443-6451. DOI: 10.1021/acsomega.9b00216. doi: 10.1021/acsomega.9b00216
[30]	Wang Y, Qin L, Chen W, et al. Novel strategies to improve tumour therapy by targeting the proteins MCT1, MCT4 and LAT1[J]. Eur J Med Chem, 2021, 226: 113806. DOI: 10.1016/j.ejmech.2021.113806. doi: 10.1016/j.ejmech.2021.113806
[31]	Zhang Y, Shi J, Liu X, et al. BAP1 links metabolic regulation of ferroptosis to tumour suppression[J]. Nat Cell Biol, 2018, 20(10): 1181-1192. DOI: 10.1038/s41556-018-0178-0. doi: 10.1038/s41556-018-0178-0 pmid: 30202049
[32]	Lang X, Green MD, Wang W, et al. Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of SLC7A11[J]. Cancer Discov, 2019, 9(12): 1673-1685. DOI: 10.1158/2159-8290.CD-19-0338. doi: 10.1158/2159-8290.CD-19-0338 pmid: 31554642
[33]	Wang W, Green M, Choi JE, et al. CD8⁺ T cells regulate tumour ferroptosis during cancer immunotherapy[J]. Nature, 2019, 569(7755): 270-274. DOI: 10.1038/s41586-019-1170-y. doi: 10.1038/s41586-019-1170-y
[34]	Lei G, Zhang Y, Koppula P, et al. The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression[J]. Cell Res, 2020, 30(2): 146-162. DOI: 10.1038/s41422-019-0263-3. doi: 10.1038/s41422-019-0263-3 pmid: 31949285
[35]	Ye LF, Chaudhary KR, Zandkarimi F, et al. Radiation-induced lipid peroxidation triggers ferroptosis and synergizes with ferroptosis inducers[J]. ACS Chem Biol, 2020, 15(2): 469-484. DOI: 10.1021/acschembio.9b00939. doi: 10.1021/acschembio.9b00939 pmid: 31899616