ArticleNature communications2017
The Shc1 adaptor simultaneously balances Stat1 and Stat3 activity to promote breast cancer immune suppression.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 62 citations in OpenAlex.
- Multi-omic Profiling of Recurrence Risk Across Breast Cancer Subtypes.medRxiv : the preprint server for health sciences · 2026Article
- The CHI3L1-neutrophil axis drives immune suppression and breast cancer metastatic dissemination.JCI insight · 2026Article
- Endoplasmic reticulum stress-related genes play a role in the prognosis of lung adenocarcinoma.Discover oncology · 2025Article
- Effects of Metformin Treatment Against Endometrial Cancer Cells Cultured In Vitro or Grafted into Female Balb/C Nude Mice: Insights into Cell Response and IGF-1R and PI3K/AKT/mTOR Signaling Pathways.Cell biochemistry and biophysics · 2025Article
- Mechanism exploration of di(2-ethylhexyl) phthalate (DEHP)-induced breast cancer via network toxicology and molecular docking analysis.Scientific reports · 2025Article
- Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy.Molecular cancer · 2025Review
- Article
- CLEC3A Promotes Immune Evasion and Tumor Progression by Enhancing PD-L1 Stability to Weaken T Cell Cytotoxicity in Luminal Breast Cancer.Breast cancer (Dove Medical Press) · 2025Article
- USP15, activated by TFAP4 transcriptionally, stabilizes SHC1 via deubiquitination and deteriorates renal cell carcinoma.Cancer science · 2024Article
- The mitochondria-related gene risk mode revealed p66Shc as a prognostic mitochondria-related gene of glioblastoma.Scientific reports · 2024Article
- p66ShcA promotes malignant breast cancer phenotypes by alleviating energetic and oxidative stress.Redox biology · 2024Article
- Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma.Nature communications · 2024Article
- STAT family of transcription factors in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Seminars in cancer biology · 2022Review
- Article
- Cytokines Activate JAK-STAT Signaling Pathway in MG-63 Cells on Titanium and Zirconia.Materials (Basel, Switzerland) · 2022Article
- The E3 ubiquitin ligase SOCS-7 reverses immunosuppression via Shc1 signaling in hepatocellular carcinoma.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- A Data Science Approach for the Identification of Molecular Signatures of Aggressive Cancers.Cancers · 2022Article
- A New Thinking: Deciphering the Aberrance and Clinical Implication of IGF Axis Regulation Pattern in Clear Cell Renal Cell Carcinoma.Frontiers in immunology · 2022Article
- The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs).Journal of immunology research · 2022Review
- Pan-Cancer Study of SHC-Adaptor Protein 1 (SHC1) as a Diagnostic, Prognostic and Immunological Biomarker in Human Cancer.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinase signalling within cancer cells is central to the establishment of an immunosuppressive microenvironment. Although tyrosine kinase inhibitors act, in part, to augment adaptive immunity, the increased heterogeneity and functional redundancy of the tyrosine kinome is a hurdle to achieving durable responses to immunotherapies. We previously identified the Shc1 (ShcA) scaffold, a central regulator of tyrosine kinase signalling, as essential for promoting breast cancer immune suppression. Herein we show that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells. Impaired Y239/Y240-ShcA phosphorylation selectively reduces STAT3 activation in breast tumours, profoundly sensitizing them to immune checkpoint inhibitors and tumour vaccines. Finally, the ability of diminished tyrosine kinase signalling to initiate STAT1-driven immune surveillance can be overcome by compensatory STAT3 hyperactivation in breast tumours. Our data indicate that inhibition of pY239/240-ShcA-dependent STAT3 signalling may represent an attractive therapeutic strategy to sensitize breast tumours to multiple immunotherapies.
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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.