ArticleMolecular cancer2015
Stromal ING1 expression induces a secretory phenotype and correlates with breast cancer patient survival.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Application and prospect of organoid technology in breast cancer.Frontiers in immunology · 2024Pooled it
- Identification of Treatment Targets in Allergic Conjunctivitis Through Proteome-Scale Mendelian Randomization Analysis.Mediators of inflammation · 2026Article
- Advances in the Research and Development of Breast Cancer Organoids.Oncology research · 2026Review
- Tissue-specific localization of the ING4 targeting subunit of the HBO1 histone acetyltransferase in the cytoplasm and nucleus of secretory cells.Histochemistry and cell biology · 2025Article
- Cancer-secreted exosomal miR-1825 induces angiogenesis to promote colorectal cancer metastasis.Cancer cell international · 2025Article
- Organoids in breast cancer translational research: intersection of technologies.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2025Review
- An integrated bioinformatics analysis of potential therapeutic targets among matrix metalloproteinases in breast cancer.Oncology letters · 2019Article
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundPrevious studies have established that levels of the Inhibitor of Growth 1(ING1) tumor suppressor are reduced in a significant proportion of different cancer types. Here we analyzed levels of ING1 in breast cancer patients to determine its prognostic significance as a biomarker for breast cancer prognosis.
methodsWe used automated quantitative analysis (AQUA) to determine the levels of ING1 in the tumor associated stromal cells of 462 breast cancer samples. To better understand how high ING1 levels affect nearby epithelium, we measured the levels of cytokines and secreted matrix metalloproteases (MMPs), using an ELISA based assay in mammary fibroblasts overexpressing ING1. These cells were also used in a 3-dimensional co-culture with MCF7 cells to determine the effect of released MMPs and other cytokines on growing colonies.
resultsWe find that high levels of ING1 in stroma are associated with tumor grade (p = 0.001) and size (p = 0.02), and inversely associated with patient survival (p = 0.0001) in luminal, but not in non-luminal cancers, suggesting that high stromal ING1 promotes cancer development. In this group of patients ING1 could also predict patient survival and act as a biomarker (HR = 2.125). While ING1 increased or decreased the expression of different cytokines, ING1 also increased the levels of MMP1, MMP3 and MMP10 by 5-8 fold, and concomitantly decreased levels of the tissue inhibitors of metalloproteases TIMP2, TIMP3 and TIMP4 by 1.5-3.3 fold, resulting in significant increases in MMP activity as determined by zymography. Co-culturing of MCF7 cells with stromal cells expressing ING1 in 3-dimensional organoid cultures suggested that MCF7 colonies were less well defined, suggesting that secreted MMPs might promote migration.
conclusionThese data indicate that stromal ING1 expression can predict the survival of patients with luminal breast cancer. High levels of ING1 in stromal cells can promote the development of breast cancer through increased expression and release of MMPs and down regulation of TIMPs, which may be an underlying mechanism of reduced patient survival.
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