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000305794 1001_ $$00000-0003-1810-170X$$aGhantous, Lucy$$b0
000305794 245__ $$aThe DNA damage response pathway regulates the expression of the immune checkpoint CD47.
000305794 260__ $$aLondon$$bSpringer Nature$$c2023
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000305794 520__ $$aCD47 is a cell surface ligand expressed on all nucleated cells. It is a unique immune checkpoint protein acting as 'don't eat me' signal to prevent phagocytosis and is constitutively overexpressed in many tumors. However, the underlying mechanism(s) for CD47 overexpression is not clear. Here, we show that irradiation (IR) as well as various other genotoxic agents induce elevated expression of CD47. This upregulation correlates with the extent of residual double-strand breaks (DSBs) as determined by γH2AX staining. Interestingly, cells lacking mre-11, a component of the MRE11-RAD50-NBS1 (MRN) complex that plays a central role in DSB repair, or cells treated with the mre-11 inhibitor, mirin, fail to elevate the expression of CD47 upon DNA damage. On the other hand, both p53 and NF-κB pathways or cell-cycle arrest do not play a role in CD47 upregualtion upon DNA damage. We further show that CD47 expression is upregulated in livers harvested from mice treated with the DNA-damage inducing agent Diethylnitrosamine (DEN) and in cisplatin-treated mesothelioma tumors. Hence, our results indicate that CD47 is upregulated following DNA damage in a mre-11-dependent manner. Chronic DNA damage response in cancer cells might contribute to constitutive elevated expression of CD47 and promote immune evasion.
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000305794 650_7 $$2NLM Chemicals$$aCD47 Antigen
000305794 650_7 $$2NLM Chemicals$$aCd47 protein, mouse
000305794 650_2 $$2MeSH$$aAnimals
000305794 650_2 $$2MeSH$$aMice
000305794 650_2 $$2MeSH$$aCD47 Antigen: genetics
000305794 650_2 $$2MeSH$$aCell Membrane
000305794 650_2 $$2MeSH$$aCell Nucleus
000305794 650_2 $$2MeSH$$aDNA Damage
000305794 650_2 $$2MeSH$$aLiver
000305794 7001_ $$aVolman, Yael$$b1
000305794 7001_ $$aHefez, Ruth$$b2
000305794 7001_ $$aWald, Ori$$b3
000305794 7001_ $$aStern, Esther$$b4
000305794 7001_ $$aFriehmann, Tomer$$b5
000305794 7001_ $$aChajut, Ayelet$$b6
000305794 7001_ $$aBremer, Edwin$$b7
000305794 7001_ $$00000-0003-4720-5735$$aElhalel, Michal Dranitzki$$b8
000305794 7001_ $$00000-0002-6662-7987$$aRachmilewitz, Jacob$$b9
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