ArticleBreast cancer research : BCR2018
Insulin-like growth factor receptor signaling in breast tumor epithelium protects cells from endoplasmic reticulum stress and regulates the tumor microenvironment.
Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- The contribution of phenolic endocrine-disrupting chemicals to breast cancer risk: A comprehensive bioinformatics analysis.Scientific reports · 2026Article
- Insulin-like growth factor 1 receptor regulates breast cancer cell adhesion through beta-1 integrin.Frontiers in endocrinology · 2026Article
- Spheroid-Based 3D Models to Decode Cell Function and Matrix Effectors in Breast Cancer.Cancers · 2025Article
- Antagonism of estrogen-related receptor-α inhibits mitochondrial oxidative phosphorylation and reduces M2 macrophage infiltration in endometrial cancer.Journal for immunotherapy of cancer · 2025Article
- Insulin-Like Growth Factor 1 Receptor Regulates Breast Cancer Cell Adhesion through Beta-1 Integrin.bioRxiv : the preprint server for biology · 2025Article
- Role of Oxidative Stress in the Occurrence, Development, and Treatment of Breast Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Breast cancer genomic analyses reveal genes, mutations, and signaling networks.Functional & integrative genomics · 2024Article
- Role of Insulin-like Growth Factor-1 Receptor in Tobacco Smoking-Associated Lung Cancer Development.Biomedicines · 2024Review
- Insulin-like growth factor-1 receptor crosstalk with integrins, cadherins, and the tumor microenvironment: sticking points in understanding IGF1R function in cancer.Endocrine-related cancer · 2023Review
- Review
- Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Endoplasmic reticulum stress targeted therapy for breast cancer.Cell communication and signaling : CCS · 2022Review
- Stromal p53 Regulates Breast Cancer Development, the Immune Landscape, and Survival in an Oncogene-Specific Manner.Molecular cancer research : MCR · 2022Article
- Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer.Cancers · 2022Article
- Decoding Insulin-Like Growth Factor Signaling Pathway From a Non-coding RNAs Perspective: A Step Towards Precision Oncology in Breast Cancer.Journal of mammary gland biology and neoplasia · 2022Review
- ActivationFrontiers in endocrinology · 2022Review
- Breast tumor IGF1R regulates cell adhesion and metastasis: alignment of mouse single cell and human breast cancer transcriptomics.Frontiers in oncology · 2022Article
- Human Breast Extracellular Matrix Microstructures and Protein Hydrogel 3D Cultures of Mammary Epithelial Cells.Cancers · 2021Article
- Chemokine signaling in cancer-stroma communications.Journal of cell communication and signaling · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundEarly analyses of human breast cancer identified high expression of the insulin-like growth factor type 1 receptor (IGF-1R) correlated with hormone receptor positive breast cancer and associated with a favorable prognosis, whereas low expression of IGF-1R correlated with triple negative breast cancer (TNBC). We previously demonstrated that the IGF-1R acts as a tumor and metastasis suppressor in the Wnt1 mouse model of TNBC. The mechanisms for how reduced IGF-1R contributes to TNBC phenotypes is unknown.
methodsWe analyzed the METABRIC dataset to further stratify IGF-1R expression with patient survival and specific parameters of TNBC. To investigate molecular events associated with the loss of IGF-1R function in breast tumor cells, we inhibited IGF-1R in human cell lines using an IGF-1R blocking antibody and analyzed MMTV-Wnt1-mediated mouse tumors with reduced IGF-1R function through expression of a dominant-negative transgene.
resultsOur analysis of the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset revealed association between low IGF-1R and reduced overall patient survival. IGF-1R expression was inversely correlated with patient survival even within hormone receptor-positive breast cancers, indicating reduced overall patient survival with low IGF-1R was not due simply to low IGF-1R expression within TNBCs. Inhibiting IGF-1R in either mouse or human tumor epithelial cells increased reactive oxygen species (ROS) production and activation of the endoplasmic reticulum stress response. IGF-1R inhibition in tumor epithelial cells elevated interleukin (IL)-6 and C-C motif chemokine ligand 2 (CCL2) expression, which was reversed by ROS scavenging. Moreover, the Wnt1/dnIGF-1R primary tumors displayed a tumor-promoting immune phenotype. The increased CCL2 promoted an influx of CD11b
conclusionsOur data support the hypothesis that reduction of IGF-1R function increases cellular stress and cytokine production to promote an aggressive tumor microenvironment through infiltration of immune cells and matrix remodeling.
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