ArticleThe Journal of clinical investigation2023
SHP2 deneddylation mediates tumor immunosuppression in colon cancer via the CD47/SIRPα axis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 66 citations in OpenAlex.
- LAIR1 suppresses phagocytosis via SHP2/USP22-mediated MYH9 degradation in glioma-associated microglia/macrophages to drive immunosuppression.British journal of cancer · 2026Article
- CD47-mediated efferocytosis in diseases: A comprehensive review.Molecular biology reports · 2026Review
- Endothelial deletion of the neddylation E2 enzyme UBE2M inhibits tumor growth by promoting nonproductive angiogenesis.The Journal of clinical investigation · 2026Article
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- CD90 mediates gastric cancer immune evasion though regulating IGF2BP2 to stabilize the m6A-CD47/SIRPα axis.Cancer cell international · 2026Article
- SHP2 as a pivotal modulator of the tumor microenvironment in gastrointestinal cancers: from mechanisms to targeted therapies.Journal of translational medicine · 2026Review
- Targeting USP14 enhances immunotherapy response by reprogramming tumor-associated macrophages in colon cancer.iScience · 2026Article
- Article
- Targeting the CD47/SIRPα interaction in cancer: opportunities in non-Hodgkin lymphoma.Expert opinion on investigational drugs · 2026Review
- Reinforced immunotherapy of M1 macrophage-derived exosomes with CEL on TNBC via regulating macrophage functions.Journal of advanced research · 2026Article
- UBE2M as a bridge spanning neddylation and cell cycle regulation in colorectal adenocarcinoma.Experimental & molecular medicine · 2026Article
- Notch-1 in macrophages promoted the ischemia-reperfusion via modulating EZH2/HSF1/BRD4/SIRPα/SHP2 induced ROS and apoptosis in cardiomyocyte.Scientific reports · 2026Article
- Perineural invasion in digestive tract tumors: Immune system interactions and therapeutic strategies.World journal of clinical oncology · 2026Review
- C-di-AMP sensitizes colorectal cancer to CD47 antibodies by activating NF-κB to promote macrophage phagocytosis.Cell communication and signaling : CCS · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Nanobody Nb07 mitigates sepsis by blocking the PFKM-p53-PD-1 axis to enhance macrophage phagocytosis.Theranostics · 2026Article
- Immunotherapy and postoperative bone defect repair strategies based on osteosarcoma tumor microenvironment characteristics: balancing antitumor effects and promotion of bone regeneration.Regenerative biomaterials · 2026Review
- The SIRP family: from structural diversity and signaling mechanisms to implications in immune-related disease targeted therapeutics.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SIPRα on macrophages binds with CD47 to resist proengulfment signals, but how the downstream signal of SIPRα controls tumor-infiltrating macrophages (TIMs) is still poorly clarified. Here, we report that the CD47/signal regulatory protein α (SIRPα) axis requires the deneddylation of tyrosine phosphatase SHP2. Mechanistically, Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) was constitutively neddylated on K358 and K364 sites; thus, its autoinhibited conformation was maintained. In response to CD47-liganded SIRPα, SHP2 was deneddylated by sentrin-specific protease 8 (SENP8), which led to the dephosphorylation of relevant substrates at the phagocytic cup and subsequent inhibition of macrophage phagocytosis. Furthermore, neddylation inactivated myeloid-SHP2 and greatly boosted the efficacy of colorectal cancer (CRC) immunotherapy. Importantly, we observed that supplementation with SHP2 allosteric inhibitors sensitized immune treatment-resistant CRC to immunotherapy. Our results emphasize that the CRC subtype that is unresponsive to immunotherapy relies on SIRPαhiSHP2hiNEDD8lo TIMs and highlight the need to further explore the strategy of SHP2 targeting in CRC therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.