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

doi:10.3969/j.issn.1674-8115.2024.06.015

Abstract

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

CLC Number:

R730.2

ZHANG Yong, LI Weihong, CHENG Zhipeng, WANG bin, WANG Siheng, WANG Yubin. Research status of receptor-interacting protein kinase 1 in regulating cancer progression and immune response[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(6): 788-794.

TrendMD

References 49

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-FLIP_L 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	HÄNGGI 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-LOURENÇO 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.

[1]	XUE Yu, ZHANG Hailong, LEI Ming. Expression of cancer-testis antigen SPANXB and its mechanism in affecting hepatocellular carcinoma progress [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(7): 801-813.
[2]	YANG Shuwen, CHEN Juan, YANG Qin, LEI Ming, HUANG Chenhui. Study on the developmental function of CT14 using the model organism Caenorhabditis elegans [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(7): 871-882.
[3]	ZHU Mingyang, XU Yuanyuan, REN Jianghao, HUANG Jiazheng, LI Ruonan, TAN Qiang. Review of sublobar resection for lung adenocarcinoma with ground-glass presence [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(7): 922-927.
[4]	FENG Xujiao, LIU Jianyue, QI Yangyang, SUN Jing, SHEN Lei. Phenotype and function of NK cell in colorectal cancer [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(6): 713-722.
[5]	YU Yang, MENG Dan, QIU Yiwen, YUAN Jian, ZHU Yingjie. Analysis of impact of type 1 diabetes on colorectal cancer by using two-sample Mendelian randomization [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(6): 755-761.
[6]	CAI Renjie, XU Ming. KHSRP regulates the responsiveness of prostate cancer cells to androgens through ANK3 [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(4): 417-426.
[7]	WANG Mengting, CHEN Yinan, XUANYUAN Xinyang, YUAN Haihua. Construction and experimental validation of mouse PDX model by malignant pleural effusion-derived tumor cells from lung cancer [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(4): 435-443.
[8]	FU Yiling, WU Qian, LUO Xiaoqing, WU Aihong, XIA Xuelan, ZHENG Min. Factors influencing advance care planning engagement behavior in patients with advanced cancer: a systematic review [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(4): 482-493.
[9]	XU Wenhui, YANG Chang, LI Ruiqing, BIAN Jing, LI Xiayi, ZHENG Leizhen. Exploratory study of interferon regulatory factor 3 promoting proliferation and invasion related to colorectal cancer cells [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(3): 301-311.
[10]	BAI Wenhui, SHEN Shukun, WU Yingli. Research progress in the anti-cancer activity and related mechanisms of arenobufagin [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(3): 385-392.
[11]	DING Yanling, LI Jie, YUAN Jun, LI Yan. Research progress in targeted therapies of chronic lymphocytic leukemia [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(2): 264-270.
[12]	JIANG Shuang, YU Jiwei. Progress of research on m⁶A demethylases in gastric cancer [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(2): 271-277.
[13]	ZHU Kaiyuan, SU Yuchen, LIU Zhichao, ZHANG Hong, LI Chunguang, ZHANG Jie, LI Zhigang. Adjuvant strategies for patients with T1b invasion after endoscopic submucosal dissection for esophageal squamous cell carcinoma [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(1): 116-123.
[14]	YANG Jingxiao, JIA Ziyao, WU Wenguang, WU Xiangsong, ZHANG Fei, LI Huaifeng, ZHU Yidi, LI Maolan. Effect of BRCA1 R1325K mutation on proliferation and apoptosis of gallbladder cancer cells [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(9): 1071-1079.
[15]	YANG Yue, HE Kaiju, ZONG Jiahao, YANG Ziyi, WU Xiangsong, GONG Wei. Diagnostic value of cell-free DNA to biliary tract cancers: a meta-analysis [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(9): 1175-1185.