ArticleBritish journal of cancer2019
Oncofoetal insulin receptor isoform A marks the tumour endothelium; an underestimated pathway during tumour angiogenesis and angiostatic treatment.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- S3RL: Enhancing Spatial Single-Cell Transcriptomics With Separable Representation Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-cell profiling of bone metastasis ecosystems reveals pivotal role of INSRTranslational oncology · 2026Article
- Therapeutic targets of formononetin for treating prostate cancer at the single-cell level.Aging · 2024Article
- Insulin receptor alternative splicing in breast and prostate cancer.Cancer cell international · 2024Review
- Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.International journal of molecular sciences · 2023Review
- Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment.Nature communications · 2022Article
- Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy.Nature communications · 2022Article
- Single-cell RNA sequencing reveals the multi-cellular ecosystem in different radiological components of pulmonary part-solid nodules.Clinical and translational medicine · 2022Article
- Insulin is expressed by enteroendocrine cells during human fetal development.Nature medicine · 2021Article
- The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation.Frontiers in pharmacology · 2021Article
- Alternative splicing in endothelial cells: novel therapeutic opportunities in cancer angiogenesis.Journal of experimental & clinical cancer research : CR · 2020Review
- A single cell atlas of the human liver tumor microenvironment.Molecular systems biology · 2020Article
- Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer.Biomolecules · 2020Review
- Manipulation of Metabolic Pathways and Its Consequences for Anti-Tumor Immunity: A Clinical Perspective.International journal of molecular sciences · 2020Review
- Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma.Nature communications · 2020Article
- IGF-binding proteins 3 and 4 are regulators of sprouting angiogenesis.Molecular biology reports · 2020Article
- Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells.Cells · 2019Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn a genomic screen for determinants of the tumour vasculature, we identified insulin receptor (INSR) to mark the tumour endothelium. As a functional role for insulin/INSR in cancer has been suggested and markers of the tumour endothelium may be attractive therapeutic targets, we investigated the role of INSR in angiogenesis.
methodsIn a genomic screen for determinants of the tumour vasculature we identified insulin receptor to mark the tumour endothelium.
resultsThe current report demonstrates the following: (i) the heavy overexpression of INSR on angiogenic vasculature in human tumours and the correlation to short survival, (ii) that INSR expression in the tumour vasculature is mainly representing the short oncofoetal and non-metabolic isoform INSR-A, (iii) the angiogenic activity of insulin on endothelial cells (EC) in vitro and in vivo, (iv) suppression of proliferation and sprouting of EC in vitro after antibody targeting or siRNA knockdown, and (v) inhibition of in vivo angiogenesis in the chicken chorioallantoic membrane (CAM) by anti-INSR antibodies. We additionally show, using preclinical mouse as well as patient data, that treatment with the inhibitor sunitinib significantly reduces the expression of INSR-A.
conclusionsThe current study underscores the oncogenic impact of INSR and suggests that targeting the INSR-A isoform should be considered in therapeutic settings.
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