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Role of Receptor Interacting Protein(rip)kinases in cancer

Genes & Diseases 2022年第6期9卷 1579-1593页

作者： Kaylee Ermine Jian Yu Lin Zhang Department of Pharmacology and Chemical Biology University of Pittsburgh School of MedicinePittsburghPA 15213USA UPMC Hillman Cancer Center PittsburghPA 15213USA Department of Pathology University of Pittsburgh School of MedicinePittsburghPA 15213USA

The Receptor Interacting Protein(rip)kinase family consists of seven Serine/Threonine kinases,which plays a key signaling role in cell survival and cell death.Each rip family member contains a conserved kinase domain and other domains that determine the specific kinase function through proteineprotein interactions.rip1 and rip3 are best known for their critical roles in necroptosis,programmed necrosis and a non-apoptotic inflammatory cell death process.Dysregulation of rip kinases contributes to a variety of pathogenic conditions such as inflammatory diseases,neurological diseases,and cancer.In cancer cells,alterations of rip kinases at genetic,epigenetic and expression levels are frequently found,and suggested to promote tumor progression and metastasis,escape of antitumor immune response,and therapeutic resistance.However,rip kinases can be either pro-tumor or anti-tumor depending on specific tumor types and cellular contexts.Therapeutic agents for targeting rip kinases have been tested in clinical trials mainly for inflammatory diseases.Deregulated expression of these kinases in different types of cancer suggests that they represent attractive therapeutic targets.The focus of this review is to outline the role of rip kinases in cancer,highlighting potential opportunities to manipulate these proteins in cancer treatment.

关键词： Cancer Cell death Immune response Necroptosis rip kinases

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