吡咯啉-5-羧酸还原酶-1在肿瘤中的作用及机制研究进展

doi:10.11904/j.issn.1002-3070.2023.03.012

实用肿瘤学杂志 ›› 2023, Vol. 37 ›› Issue (3): 267-271.doi: 10.11904/j.issn.1002-3070.2023.03.012

吡咯啉-5-羧酸还原酶-1在肿瘤中的作用及机制研究进展

周波蓉, 宋雅楠综述, 夏伟审校

上海中医药大学附属第七人民医院核医学科(上海 200137)

收稿日期:2023-04-25 修回日期:2023-07-05 出版日期:2023-06-28 发布日期:2023-08-07
通讯作者: 夏伟,E-mail:awingxia@163.com
作者简介:周波蓉,女,(1998-),硕士研究生,从事肿瘤综合治疗的影像学评价及机制的研究。
基金资助:
上海市浦东新区卫生系统领先人才培养计划(编号:PWRI2019-03);上海市浦东新区科技发展基金民生科研专项(编号:PKJ2021-Y04);上海市科学技术委员会生物医药科技支撑专项(编号:20S21901900)

Research progress on the role and mechanism of pyrrolin-5-carboxylate reductase-1 in tumor

ZHOU Borong, SONG Yanan, XIA Wei

Department of Nuclear Medicine,The Seventh People's Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200137,China

Received:2023-04-25 Revised:2023-07-05 Online:2023-06-28 Published:2023-08-07

摘要/Abstract

摘要： 吡咯啉-5-羧酸还原酶-1(Pyrroline-5-Carboxylate Reductase-1,PYCR1)是线粒体脯氨酸合成的关键酶。越来越多的研究表明PYCR1在多种恶性肿瘤中高表达,影响肿瘤细胞增殖、凋亡、侵袭和迁移等生物学行为,且与临床预后密切相关,有望成为新的肿瘤生物标志物,但其涉及的作用机制比较复杂。本文将从PYCR1在肿瘤中的作用机制、临床意义以及PYCR1抑制剂对肿瘤的影响三个方面综述PYCR1在肿瘤发生发展中的作用。

关键词: PYCR1, 脯氨酸, 肿瘤, 作用机制

Abstract: Pyrroline-5-Carboxylate Reductase-1(PYCR1)is a key enzyme for synthesis of mitochondrial proline.More and more studies have shown that PYCR1 is highly expressed in various malignant tumors,affecting the biological behaviors such as tumor cell proliferation,apoptosis,invasion and migration,and is closely related to clinical prognosis.It is expected to become a new tumor biomarker,but its mechanism of action is relatively complex.This article will review the role of PYCR1 in tumorigenesis and development from three aspects: its mechanism of action,clinical significance and the effect of PYCR1 inhibitors on tumors.

Key words: PYCR1, Proline, Tumor, Mechanism of action

中图分类号:

R730.1

周波蓉, 宋雅楠, 夏伟. 吡咯啉-5-羧酸还原酶-1在肿瘤中的作用及机制研究进展[J]. 实用肿瘤学杂志, 2023, 37(3): 267-271.

ZHOU Borong, SONG Yanan, XIA Wei. Research progress on the role and mechanism of pyrrolin-5-carboxylate reductase-1 in tumor[J]. Journal of Practical Oncology, 2023, 37(3): 267-271.

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链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2023.03.012

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2023/V37/I3/267

参考文献

1 Christensen EM,Patel SM,Korasick DA,et al.Resolving the cofactor-binding site in the proline biosynthetic enzyme human pyrroline-5-carboxylate reductase 1[J].J Biol Chem,2017,292(17):7233-7243.
2 D′Aniello C,Patriarca EJ,Phang JM,et al.Proline metabolism in tumor growth and metastatic progression[J].Front Oncol,2020,10:776.
3 Phang JM.Proline metabolism in cell regulation and cancer biology:Recent advances and hypotheses[J].Antioxid Redox Signal,2019,30(4):635-649.
4 Gao Y,Luo L,Xie Y,et al.PYCR1 knockdown inhibits the proliferation,migration,and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma[J].Mol Carcinog,2020,59(5):503-511.
5 Bogner AN,Stiers KM,Tanner JJ.Structure,biochemistry,and gene expression patterns of the proline biosynthetic enzyme pyrroline-5-carboxylate reductase(PYCR),an emerging cancer therapy target[J].Amino Acids,2021,53(12):1817-1834.
6 Bonnay F,Veloso A,Steinmann V,et al.Oxidative metabolism drives immortalization of neural stem cells during tumorigenesis[J].Cell,2020,182(6):1490-1507.
7 Liu W,Hancock CN,Fischer JW,et al.Proline biosynthesis augments tumor cell growth and aerobic glycolysis:involvement of pyridine nucleotides[J].Sci Rep.2015,5:17206.
8 Westbrook RL,Bridges E,Roberts J,et al.Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions[J].Cell Rep,2022,38(5):110320.
9 Oudaert I,Satilmis H,Vlummens P,et al.Pyrroline-5-carboxylate reductase 1:a novel target for sensitizing multiple myeloma cells to bortezomib by inhibition of PRAS40-mediated protein synthesis[J].J Exp Clin Cancer Res,2022,41(1):45.
10 Chen K,Guo L,Wu C.How signaling pathways link extracellular mechano-environment to proline biosynthesis:A hypothesis:PINCH-1 and kindlin-2 sense mechanical signals from extracellular matrix and link them to proline biosynthesis[J].Bioessays,2021,43(9):e2100116.
11 Zhang J,Shang L,Jiang W,et al.Shikonin induces apoptosis and autophagy via downregulation of pyrroline-5-carboxylate reductase1 in hepatocellular carcinoma cells[J].Bioengineered,2022,13(3):7904-7918.
12 Guo J,Cheng X,Tian Y,et al.Knockdown of PYCR1 suppressed the malignant phenotype of human hepatocellular carcinoma cells via inhibiting the AKT pathway activation[J].Reprod Biol,2021,21(3):100534.
13 Xiao S,Li S,Yuan Z,et al.Pyrroline-5-carboxylate reductase 1(PYCR1)upregulation contributes to gastric cancer progression and indicates poor survival outcome[J].Ann Transl Med,2020,8(15):937.
14 Du S,Sui Y,Ren W,et al.PYCR1 promotes bladder cancer by affecting the Akt/Wnt/β-catenin signaling[J].J Bioenerg Biomembr,2021,53(2):247-258.
15 Cheng C,Song D,Wu Y,et al.RAC3 promotes proliferation,migration and invasion via PYCR1/JAK/STAT signaling in bladder cancer[J].Front Mol Biosci,2020,7:218.
16 Yan K,Xu X,Wu T,et al.Knockdown of PYCR1 inhibits proliferation,drug resistance and EMT in colorectal cancer cells by regulating STAT3-Mediated p38 MAPK and NF-κB signalling pathway[J].Biochem Biophys Res Commun,2019,520(2):486-491.
17 Wei X,Zhang X,Wang S,et al.PYCR1 regulates glutamine metabolism to construct an immunosuppressive microenvironment for the progression of clear cell renal cell carcinoma[J].Am J Cancer Res,2022,12(8):3780-3798.
18 Li H,Ning S,Ghandi M,et al.The landscape of cancer cell line metabolism[J].Nat Med,2019,25(5):850-860.
19 Xiao S,Yao X,Ye J,et al.Epigenetic modification facilitates proline synthase PYCR1 aberrant expression in gastric cancer[J].Biochim Biophys Acta Gene Regul Mech,2022,1865(6):194829.
20 Song W,Yang K,Luo J,et al.Dysregulation of USP18/FTO/PYCR1 signaling network promotes bladder cancer development and progression[J].Aging(Albany NY),2021,13(3):3909-3925.
21 Chen S,Yang X,Yu M,et al.SIRT3 regulates cancer cell proliferation through deacetylation of PYCR1 in proline metabolism[J].Neoplasia,2019,21(7):665-675.
22 Guo L,Cui C,Wang J,et al.PINCH-1 regulates mitochondrial dynamics to promote proline synthesis and tumor growth[J].Nat Commun,2020,11(1):4913.
23 Phang JM,Liu W,Hancock CN,et al.Proline metabolism and cancer:emerging links to glutamine and collagen[J].Curr Opin Clin Nutr Metab Care,2015,18(1):71-77.
24 Kuo CL,Chou HY,Chiu YC,et al.Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis[J].Cancer Lett,2020,474:138-150.
25 Xu Y,Zuo W,Wang X,et al.Deciphering the effects of PYCR1 on cell function and its associated mechanism in hepatocellular carcinoma[J].Int J Biol Sci,2021,17(9):2223-2239.
26 Wang H,Mao W,Lou W,et al.PYCR1:A potential prognostic biomarker in pancreatic ductal adenocarcinoma[J].J Cancer,2022,13(5):1501-1511.
27 Liu Z,Sun T,Zhang Z,et al.An 18-gene signature based on glucose metabolism and DNA methylation improves prognostic prediction for urinary bladder cancer[J].Genomics,2021,113(1 Pt 2):896-907.
28 She Y,Mao A,Li F,et al.P5CR1 protein expression and the effect of gene-silencing on lung adenocarcinoma[J].PeerJ,2019,7:e6934.
29 Shenoy A,Belugali Nataraj N,Perry G,et al.Proteomic patterns associated with response to breast cancer neoadjuvant treatment[J].Mol Syst Biol,2020,16(9):e9443.
30 Liu W,Wang Q,Chang J.Global metabolomic profiling of trastuzumab resistant gastric cancer cells reveals major metabolic pathways and metabolic signatures based on UHPLC-Q exactive-MS/MS[J].RSC Adv,2019,9(70):41192-41208.
31 Wu Y,Zhang X,Wei X,et al.A mitochondrial dysfunction and oxidative stress pathway-based prognostic signature for clear cell renal cell carcinoma[J].Oxid Med Cell Longev,2021,2021:9939331.
32 Zhou B,Mai Z,Ye Y,et al.The role of PYCR1 in inhibiting 5-fluorouracil-induced ferroptosis and apoptosis through SLC25A10 in colorectal cancer[J].Hum Cell,2022,35(6):1900-1911.
33 Milne K,Sun J,Zaal EA,et al.A fragment-like approach to PYCR1 inhibition[J].Bioorg Med Chem Lett,2019,29(18):2626-2631.
34 Christensen EM,Bogner AN,Vandekeere A,et al.In crystallo screening for proline analog inhibitors of the proline cycle enzyme PYCR1[J].J Biol Chem,2020,295(52):18316-18327.
35 Forlani G,Sabbioni G,Ragno D,et al.Phenyl-substituted aminomethylene-bisphosphonates inhibit human P5C reductase and show antiproliferative activity against proline-hyperproducing tumour cells[J].J Enzyme Inhib Med Chem,2021,36(1):1248-1257.

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吡咯啉-5-羧酸还原酶-1在肿瘤中的作用及机制研究进展

Research progress on the role and mechanism of pyrrolin-5-carboxylate reductase-1 in tumor

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