Necroptosis and Cancer

Overview

Journal Trends Cancer

Publisher Cell Press

Specialty Oncology

Date 2017 Apr 29

PMID 28451648

Citations 119

Authors

Ayaz Najafov

Hongbo Chen

Junying Yuan

Affiliations

Soon will be listed here.

Abstract

Necroptosis is a programmed lytic cell death pathway, deregulation of which is linked to various inflammatory disorders. Escape from programmed cell death and inflammation play a significant role in cancer, and therefore, investigating the role of necroptosis in cancer has been of high interest. Necroptosis has been shown to promote cancer metastasis and T cells death. Escape from necroptosis via loss of RIPK3 expression is a feature of some cancers. While necroptosis is a promising novel target for cancer therapies, further investigation into its biological role in carcinogenesis is warranted. In this article, we review the recently-identified interplay points between necroptosis and cancer, and outline major biological questions that require further inquiry on the road to targeting this pathway in cancer.

Citing Articles

Machine learning-based bulk RNA analysis reveals a prognostic signature of 13 cell death patterns and potential therapeutic target of SMAD3 in acute myeloid leukemia.

Bao X, Chen Y, Chang J, Du J, Yang C, Wu Y BMC Cancer. 2025; 25(1):273.

PMID: 39955536 PMC: 11830216. DOI: 10.1186/s12885-025-13658-3.

Advances in non-apoptotic regulated cell death: implications for malignant tumor treatment.

Zhang Y, Yi S, Luan M Front Oncol. 2025; 15:1519119.

PMID: 39949740 PMC: 11821507. DOI: 10.3389/fonc.2025.1519119.

A novel necroptosis-related genes signature to predict prognosis and treatment response in bladder cancer.

Yao D, Yu W, Ma X, Tian J Front Mol Biosci. 2024; 11:1493411.

PMID: 39655212 PMC: 11625674. DOI: 10.3389/fmolb.2024.1493411.

Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review.

Saxena R, Welsh C, He Y Front Cell Dev Biol. 2024; 12:1462339.

PMID: 39620145 PMC: 11604647. DOI: 10.3389/fcell.2024.1462339.

Lin C, Lin K, Lin X, Yuan H, Zhang Y, Xie Z Transl Lung Cancer Res. 2024; 13(10):2713-2728.

PMID: 39507021 PMC: 11535849. DOI: 10.21037/tlcr-24-627.

References

Ito Y, Ofengeim D, Najafov A, Das S, Saberi S, Li Y . RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science. 2016; 353(6299):603-8. PMC: 5444917. DOI: 10.1126/science.aaf6803. View

Cho Y, Challa S, Moquin D, Genga R, Ray T, Guildford M . Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009; 137(6):1112-23. PMC: 2727676. DOI: 10.1016/j.cell.2009.05.037. View

Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C, Wachsmuth L . RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature. 2014; 513(7516):90-4. PMC: 4206266. DOI: 10.1038/nature13608. View

Berger S, Kasparcova V, Hoffman S, Swift B, Dare L, Schaeffer M . Cutting Edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice. J Immunol. 2014; 192(12):5476-80. PMC: 4048763. DOI: 10.4049/jimmunol.1400499. View

Brumatti G, Ma C, Lalaoui N, Nguyen N, Navarro M, Tanzer M . The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia. Sci Transl Med. 2016; 8(339):339ra69. DOI: 10.1126/scitranslmed.aad3099. View

Bonnet M, Preukschat D, Welz P, van Loo G, Ermolaeva M, Bloch W . The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation. Immunity. 2011; 35(4):572-82. DOI: 10.1016/j.immuni.2011.08.014. View

Ofengeim D, Yuan J . Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death. Nat Rev Mol Cell Biol. 2013; 14(11):727-36. DOI: 10.1038/nrm3683. View

Murphy J, Czabotar P, Hildebrand J, Lucet I, Zhang J, Alvarez-Diaz S . The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity. 2013; 39(3):443-53. DOI: 10.1016/j.immuni.2013.06.018. View

Chen X, Li W, Ren J, Huang D, He W, Song Y . Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res. 2013; 24(1):105-21. PMC: 3879712. DOI: 10.1038/cr.2013.171. View

10.

Sun L, Wang H, Wang Z, He S, Chen S, Liao D . Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012; 148(1-2):213-27. DOI: 10.1016/j.cell.2011.11.031. View

11.

Welz P, Wullaert A, Vlantis K, Kondylis V, Fernandez-Majada V, Ermolaeva M . FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature. 2011; 477(7364):330-4. DOI: 10.1038/nature10273. View

12.

Wu Y, Zhou B . Inflammation: a driving force speeds cancer metastasis. Cell Cycle. 2009; 8(20):3267-73. PMC: 3702728. DOI: 10.4161/cc.8.20.9699. View

13.

LaCasse E, Mahoney D, Cheung H, Plenchette S, Baird S, Korneluk R . IAP-targeted therapies for cancer. Oncogene. 2008; 27(48):6252-75. DOI: 10.1038/onc.2008.302. View

14.

Zhou W, Yuan J . SnapShot: Necroptosis. Cell. 2014; 158(2):464-464.e1. DOI: 10.1016/j.cell.2014.06.041. View

15.

Hitomi J, Christofferson D, Ng A, Yao J, Degterev A, Xavier R . Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell. 2008; 135(7):1311-23. PMC: 2621059. DOI: 10.1016/j.cell.2008.10.044. View

16.

Wu W, Zhu H, Fu Y, Shen W, Xu J, Miao K . Clinical significance of down-regulated cylindromatosis gene in chronic lymphocytic leukemia. Leuk Lymphoma. 2013; 55(3):588-94. DOI: 10.3109/10428194.2013.809077. View

17.

Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G . CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. Nature. 2003; 424(6950):793-6. DOI: 10.1038/nature01803. View

18.

Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S . Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2001; 1(6):489-95. DOI: 10.1038/82732. View

19.

Pobezinskaya Y, Kim Y, Choksi S, Morgan M, Li T, Liu C . The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors. Nat Immunol. 2008; 9(9):1047-54. PMC: 2577920. DOI: 10.1038/ni.1639. View

20.

He L, Peng K, Liu Y, Xiong J, Zhu F . Low expression of mixed lineage kinase domain-like protein is associated with poor prognosis in ovarian cancer patients. Onco Targets Ther. 2013; 6:1539-43. PMC: 3817086. DOI: 10.2147/OTT.S52805. View