ArticleThe Journal of clinical investigation2022
SIRPγ-expressing cancer stem-like cells promote immune escape of lung cancer via Hippo signaling.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- A Multistep Immune-Competent Genetically Engineered Mouse Model Reveals Phenotypic Plasticity in Uveal Melanoma.Cancer research · 2026Article
- SIRPγ limits effector differentiation of human CD8 T cells in response to subthreshold TCR-signaling.ImmunoHorizons · 2026Article
- Immune escape mechanism in lung adenocarcinoma.Chinese medical journal · 2026Article
- The SIRP family: from structural diversity and signaling mechanisms to implications in immune-related disease targeted therapeutics.Frontiers in immunology · 2026Review
- UBA1 enhances phagocytosis by suppressing CD47 expression in small cell lung cancer.Frontiers in oncology · 2026Article
- Profiling of the mycobiome and metabolome: a comparative study of benign pulmonary nodules and lung adenocarcinoma.Frontiers in cellular and infection microbiology · 2026Article
- CD146Theranostics · 2026Article
- SIRPB1 is transcriptionally regulated by USF2 and promotes cutaneous malignant melanoma tumorigenicity through SOCS1/STAT3 signaling.iScience · 2025Article
- Transcriptomic analysis reveals the potential role of TOE1 in hepatocellular carcinoma.Scientific reports · 2025Article
- Targeting AQP5-mediated arginine deprivation in gastric cancer stem cells restores NK cell anti-tumor immunity.Cell reports. Medicine · 2025Article
- FADD Activation in Hepatocellular Carcinoma Potentiates CD8+ T-cell Responses and Sensitizes to Immune Checkpoint Inhibitors.Cancer research · 2025Article
- Scaffolding Protein ENH Promotes Tumor Angiogenesis and Growth Through Macrophage Recruitment and Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ST6GALNAC1 mediates sialylation of mucins in non-small cell lung cancer to evade immune surveillance.Journal of thoracic disease · 2025Article
- P4HA1 mediates YAP hydroxylation and accelerates collagen synthesis in temozolomide-resistant glioblastoma.Chinese medical journal · 2025Article
- SNRPB/CCNB1 axis promotes hepatocellular carcinoma progression and cisplatin resistance through enhancing lipid metabolism reprogramming.Journal of experimental & clinical cancer research : CR · 2025Article
- SIRPγ modulates effector differentiation of human CD8 T Cells under suboptimal TCR stimulation: implications for immune homeostasis and autoimmunity.bioRxiv : the preprint server for biology · 2025Article
- Identification of clusters related to programmed cell death and potential prognostic biomarkers for immunotherapy response in endometrial cancer.Scientific reports · 2025Article
- Cancer stem cells: Bridging microenvironmental interactions and clinical therapy.Clinical and translational medicine · 2025Review
- A multi-step immune-competent genetic mouse model reveals phenotypic plasticity in uveal melanoma.bioRxiv : the preprint server for biology · 2025Article
- ALDH4A1 functions as an active component of the MPC complex maintaining mitochondrial pyruvate import for TCA cycle entry and tumour suppression.Nature cell biology · 2025Article
Corrections and comments
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Authors and funding
33 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγhi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγhi and SIRPγlo/- tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγhi cells serve as CSLCs and tumor immune checkpoint-initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy.
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