上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2024 , Vol. 44 >Issue 6: 788 - 794

DOI: https://doi.org/10.3969/j.issn.1674-8115.2024.06.015

综述

受体相互作用蛋白激酶1调节癌症进展和免疫反应的研究现状

  • 张勇 ,
  • 李伟宏 ,
  • 程志鹏 ,
  • 王斌 ,
  • 王思珩 ,
  • 王毓斌
展开
  • 1.山西医科大学第五临床医学院，太原 030012
    2.山西医科大学附属山西省人民医院泌尿外科，太原 030012
张 勇（1997—），男，硕士生；电子信箱：840595873@qq.com。
王毓斌，电子信箱：wangyb1980@163.com。

收稿日期: 2024-01-09

  录用日期: 2024-04-12

  网络出版日期: 2024-06-28

基金资助

山西省自然科学研究项目(202103021224375);山西省留学人员科技活动择优资助项目(2022047);山西省回国留学人员科研资助项目(2022-204)

收起

Research status of receptor-interacting protein kinase 1 in regulating cancer progression and immune response

  • Yong ZHANG ,
  • Weihong LI ,
  • Zhipeng CHENG ,
  • bin WANG ,
  • Siheng WANG ,
  • Yubin WANG
Expand
  • 1.The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan 030012, China
    2.Department of Urology, Shanxi Provincial People′s Hospital, Shanxi Medical University, Taiyuan 030012, China
WANG Yubin, E-mail: wangyb1980@163.com.

Received date: 2024-01-09

  Accepted date: 2024-04-12

  Online published: 2024-06-28

Supported by

Natural Science Foundation of Shanxi Province(202103021224375);Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province(2022047);Research Project Supported by Shanxi Scholarship Council of China(2022-204)

Fold

摘要

受体相互作用蛋白激酶1（receptor-interacting protein kinase 1，RIPK1）是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质，引起下游的信号转导和生物效应。近年来，随着对RIPK1的深入研究，学者发现其在自身免疫性疾病、神经退行性疾病，以及多种实体瘤和血液肿瘤中具有重要意义。一方面，RIPK1通过激活特定通路如核因子-κB（nuclear factor-κB，NF-κB）和丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）等促进细胞存活及炎症反应。另一方面，RIPK1通过与胱天蛋白酶-8（cysteinyl aspartate specific proteinase-8，caspase-8）作用促进凋亡，或与RIPK3和混合谱系激酶结构域样假激酶（mixed lineage kinase domain-like protein，MLKL）作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展，也可以启动机体适应性免疫，抑制肿瘤进展；此外，还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现，可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手，深入探讨其功能，特别是其在调节癌症进展和免疫反应方面的功能，为癌症靶向药物的开发提供新的思路。

关键词： 受体相互作用蛋白激酶1; 坏死性凋亡; 坏死复合物; 癌症; 免疫反应; 靶向治疗

本文引用格式

张勇 , 李伟宏 , 程志鹏 , 王斌 , 王思珩 , 王毓斌 . 受体相互作用蛋白激酶1调节癌症进展和免疫反应的研究现状[J]. 上海交通大学学报（医学版）, 2024 , 44(6) : 788 -794 . DOI: 10.3969/j.issn.1674-8115.2024.06.015

Abstract

Receptor-interacting protein kinase 1 (RIPK1) is a multi-domain serine/threonine protein kinase that causes downstream signal transduction and biological effects by phosphorylating specific proteins. In recent years, with the in-depth study of RIPK1, scholars have found that it is of great significance in autoimmune diseases, neurodegenerative diseases, and a variety of solid tumors and hematological tumors. On the one hand, RIPK1 promotes cell survival and inflammatory responses by activating specific pathways such as nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). On the other hand, RIPK1 promotes apoptosis by interacting with cysteinyl aspartate specific proteinase-8 (caspase-8), or promotes necroptosis by interacting with RIPK3 and mixed lineage kinase domain-like protein (MLKL). As an upstream signal, RIPK1 has different expression levels in patients with different tumors. Its scaffold function and kinase activity can regulate cancer progression, initiate adaptive immunity, inhibit tumor progression, and generate an immunosuppressive tumor microenvironment to promote tumor development. Its dual role has been demonstrated in regulating the occurrence and development of tumors and the body's immune response, and can be used as a new therapeutic target to control cancer progression. This paper starts with the structure of RIPK1 to further explore its function in regulating cancer progression and immune response, and to provide new ideas for the development of cancer-targeted drugs.

Key words： receptor-interacting protein kinase 1 (RIPK1); necrotizing apoptosis; necrotic complex; cancer; immune response; targeted therapy

参考文献

1 DEGTEREV A, HUANG Z H, BOYCE M, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury[J]. Nat Chem Biol, 2005, 1(2): 112-119.
2 SHAN B, PAN H L, NAJAFOV A, et al. Necroptosis in development and diseases[J]. Genes Dev, 2018, 32(5/6): 327-340.
3 DOVEY C M, DIEP J, CLARKE B P, et al. MLKL requires the inositol phosphate code to execute necroptosis[J]. Mol Cell, 2018, 70(5): 936-948.e7.
4 SEIFERT L, WERBA G, TIWARI S, et al. The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression[J]. Nature, 2016, 532(7598): 245-249.
5 KONDYLIS V, PASPARAKIS M. RIP kinases in liver cell death, inflammation and cancer[J]. Trends Mol Med, 2019, 25(1): 47-63.
6 YAN J, WAN P X, CHOKSI S, et al. Necroptosis and tumor progression[J]. Trends Cancer, 2022, 8(1): 21-27.
7 MIFFLIN L, OFENGEIM D, YUAN J Y. Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target[J]. Nat Rev Drug Discov, 2020, 19(8): 553-571.
8 LI W J, YUAN J Y. Targeting RIPK1 kinase for modulating inflammation in human diseases[J]. Front Immunol, 2023, 14: 1159743.
9 HE S D, WANG X D. RIP kinases as modulators of inflammation and immunity[J]. Nat Immunol, 2018, 19(9): 912-922.
10 RIEBELING T, KUNZENDORF U, KRAUTWALD S. The role of RHIM in necroptosis[J]. Biochem Soc Trans, 2022, 50(4): 1197-1205.
11 WU G W, LI D K, LIANG W, et al. PP6 negatively modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPL to promote TNFα-mediated cell death[J]. Cell Death Dis, 2022, 13(9): 773.
12 DRABER P, KUPKA S, REICHERT M, et al. LUBAC-recruited CYLD and A20 regulate gene activation and cell death by exerting opposing effects on linear ubiquitin in signaling complexes[J]. Cell Rep, 2015, 13(10): 2258-2272.
13 YUAN J Y, AMIN P, OFENGEIM D. Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases[J]. Nat Rev Neurosci, 2019, 20(1): 19-33.
14 DONDELINGER Y, DARDING M, BERTRAND M J, et al. Poly-ubiquitination in TNFR1-mediated necroptosis[J]. Cell Mol Life Sci, 2016, 73(11/12): 2165-2176.
15 XU D C, JIN T J, ZHU H, et al. TBK1 suppresses RIPK1-driven apoptosis and inflammation during development and in aging[J]. Cell, 2018, 174(6): 1477-1491.e19.
16 WERTZ I, DIXIT V. A20: a bipartite ubiquitin editing enzyme with immunoregulatory potential[J]. Adv Exp Med Biol, 2014, 809: 1-12.
17 GONG Y T, FAN Z Y, LUO G P, et al. The role of necroptosis in cancer biology and therapy[J]. Mol Cancer, 2019, 18(1): 100.
18 LI X M, LI F, ZHANG X X, et al. Caspase-8 auto-cleavage regulates programmed cell death and collaborates with RIPK3/MLKL to prevent lymphopenia[J]. Cell Death Differ, 2022, 29(8): 1500-1512.
19 SALEH D, NAJJAR M, ZELIC M, et al. Kinase activities of RIPK1 and RIPK3 can direct IFN-β synthesis induced by lipopolysaccharide[J]. J Immunol, 2017, 198(11): 4435-4447.
20 LINKERMANN A, GREEN D R. Necroptosis[J]. N Engl J Med, 2014, 370(5): 455-465.
21 LIU T J, ZONG H F, CHEN X Y, et al. Toll-like receptor 4-mediated necroptosis in the development of necrotizing enterocolitis[J]. Pediatr Res, 2022, 91(1): 73-82.
22 BRISSE M, LY H. Comparative structure and function analysis of the RIG-I-like receptors: RIG-I and MDA5[J]. Front Immunol, 2019, 10: 1586.
23 ZHANG T, YIN C R, BOYD D F, et al. Influenza virus Z-RNAs induce ZBP1-mediated necroptosis[J]. Cell, 2020, 180(6): 1115-1129.e13.
24 LIN J, KUMARI S, KIM C, et al. RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation[J]. Nature, 2016, 540(7631): 124-128.
25 DEGTEREV A, OFENGEIM D, YUAN J Y. Targeting RIPK1 for the treatment of human diseases[J]. Proc Natl Acad Sci U S A, 2019, 116(20): 9714-9722.
26 DILLON C P, WEINLICH R, RODRIGUEZ D A, et al. RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3[J]. Cell, 2014, 157(5): 1189-1202.
27 IMANISHI T, UNNO M, YONEDA N, et al. RIPK1 blocks T cell senescence mediated by RIPK3 and caspase-8[J]. Sci Adv, 2023, 9(4): eadd6097.
28 YATIM N, JUSFORGUES-SAKLANI H, OROZCO S, et al. RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8? T cells[J]. Science, 2015, 350(6258): 328-334.
29 MANDAL R, BARRóN J C, KOSTOVA I, et al. Caspase-8: the double-edged sword[J]. Biochim Biophys Acta Rev Cancer, 2020, 1873(2): 188357.
30 WU B Y, LI J Y, WANG H, et al. RIPK1 is aberrantly expressed in multiple B-cell cancers and implicated in the underlying pathogenesis[J]. Discov Oncol, 2023, 14(1): 131.
31 CAO L Y, MU W. Necrostatin-1 and necroptosis inhibition: pathophysiology and therapeutic implications[J]. Pharmacol Res, 2021, 163: 105297.
32 KATSUYA K, OIKAWA D, IIO K, et al. Small-molecule inhibitors of linear ubiquitin chain assembly complex (LUBAC), HOIPINs, suppress NF- κB signaling[J]. Biochem Biophys Res Commun, 2019, 509(3): 700-706.
33 WANG Y K, MA N, XU S, et al. PPDPF suppresses the development of hepatocellular carcinoma through TRIM21-mediated ubiquitination of RIPK1[J]. Cell Rep, 2023, 42(4): 112340.
34 JUNG S Y, PARK J I, JEONG J H, et al. Receptor interacting protein 1 knockdown induces cell death in liver cancer by suppressing STAT3/ATR activation in a p53-dependent manner[J]. Am J Cancer Res, 2022, 12(6): 2594-2611.
35 YU Y Q, THONN V, PATANKAR J V, et al. SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth[J]. Cell Death Dis, 2022, 13(1): 52.
36 LIN P H, LIN C L, HE R F, et al. TRAF6 regulates the abundance of RIPK1 and inhibits the RIPK1/RIPK3/MLKL necroptosis signaling pathway and affects the progression of colorectal cancer[J]. Cell Death Dis, 2023, 14(1): 6.
37 BAI W Q, CUI F J, WANG Z H, et al. Receptor-interacting protein kinase 1 (RIPK1) regulates cervical cancer cells via NF-κB-TNF-α pathway: an in vitro study[J]. Transl Oncol, 2023, 36: 101748.
38 KHAMSEH M E, SHEIKHI A, SHAHSAVARI Z, et al. Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas[J]. BMC Endocr Disord, 2022, 22(1): 1.
39 PATEL S, WEBSTER J D, VARFOLOMEEV E, et al. RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases[J]. Cell Death Differ, 2020, 27(1): 161-175.
40 H?NGGI K, VASILIKOS L, VALLS A F, et al. RIPK1/RIPK3 promotes vascular permeability to allow tumor cell extravasation independent of its necroptotic function[J]. Cell Death Dis, 2017, 8(2): e2588.
41 LI Y S, XIONG Y, ZHANG G, et al. Identification of 5-(2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as a new class of receptor-interacting protein kinase 1 (RIPK1) inhibitors, which showed potent activity in a tumor metastasis model[J]. J Med Chem, 2018, 61(24): 11398-11414.
42 ZHU G W, DU Q, CHEN X, et al. Receptor-interacting serine/threonine-protein kinase 1 promotes the progress and lymph metastasis of gallbladder cancer[J]. Oncol Rep, 2019, 42(6): 2435-2449.
43 MCCORMICK K D, GHOSH A, TRIVEDI S, et al. Innate immune signaling through differential RIPK1 expression promote tumor progression in head and neck squamous cell carcinoma[J]. Carcinogenesis, 2016, 37(5): 522-529.
44 CUCHET-LOUREN?O D, ELETTO D, WU C X, et al. Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation[J]. Science, 2018, 361(6404): 810-813.
45 LI Y, FüHRER M, BAHRAMI E, et al. Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases[J]. Proc Natl Acad Sci U S A, 2019, 116(3): 970-975.
46 LALAOUI N, BOYDEN S E, ODA H, et al. Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease[J]. Nature, 2020, 577(7788): 103-108.
47 TAO P F, SUN J Q, WU Z M, et al. A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1[J]. Nature, 2020, 577(7788): 109-114.
48 AAES T L, KACZMAREK A, DELVAEYE T, et al. Vaccination with necroptotic cancer cells induces efficient anti-tumor immunity[J]. Cell Rep, 2016, 15(2): 274-287.
49 CUCOLO L, CHEN Q Z, QIU J Y, et al. The interferon-stimulated gene RIPK1 regulates cancer cell intrinsic and extrinsic resistance to immune checkpoint blockade[J]. Immunity, 2022, 55(4): 671-685.e10.
Options
文章导航

/

〈 〉