ArticleNeoplasia (New York, N.Y.)2015
Function of Integrin-Linked Kinase in Modulating the Stemness of IL-6-Abundant Breast Cancer Cells by Regulating γ-Secretase-Mediated Notch1 Activation in Caveolae.
Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Unlocking the Therapeutic Potential of Integrin-Linked Kinase Inhibitors in Bioengineered 3D Breast Tumor Stroma Models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Notch1 regulates Orai1 and Orai3 expression in breast cancer cells.Scientific reports · 2025Article
- Cancer Stem Cells from Definition to Detection and Targeted Drugs.International journal of molecular sciences · 2024Review
- ILK inhibition reduces osteophyte formation through suppression of osteogenesis in BMSCs via Akt/GSK-3β/β-catenin pathway.Molecular biology reports · 2024Article
- Endothelial cells metabolically regulate breast cancer invasion toward a microvessel.APL bioengineering · 2023Article
- Dihydroconiferyl Ferulate Isolated fromPharmaceuticals (Basel, Switzerland) · 2022Article
- Caveolin1: its roles in normal and cancer stem cells.Journal of cancer research and clinical oncology · 2021Review
- Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents.Signal transduction and targeted therapy · 2021Review
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
- Understanding the role of integrins in breast cancer invasion, metastasis, angiogenesis, and drug resistance.Oncogene · 2021Review
- Breast cancer stem cells: A review of their characteristics and the agents that affect them.Molecular carcinogenesis · 2021Review
- The focal adhesion protein Integrin-Linked Kinase (ILK) as an important player in breast cancer pathogenesis.Cell adhesion & migration · 2020Review
- Review
- Research progress of cancer stem cells and IL-6/STAT3 signaling pathway in esophageal adenocarcinoma.Translational cancer research · 2020Review
- A "NOTCH" Deeper into the Epithelial-To-Mesenchymal Transition (EMT) Program in Breast Cancer.Genes · 2019Review
- β1 Integrin is essential for fascin-mediated breast cancer stem cell function and disease progression.International journal of cancer · 2019Article
- ILK promotes survival and self-renewal of hypoxic MSCs via the activation of lncTCF7-Wnt pathway induced by IL-6/STAT3 signaling.Gene therapy · 2019Article
- Smooth Muscle Contact Drives Endothelial Regeneration by BMPR2-Notch1-Mediated Metabolic and Epigenetic Changes.Circulation research · 2019Article
- Age-related focal loss of contractile vascular smooth muscle cells in retinal arterioles is accelerated by caveolin-1 deficiency.Neurobiology of aging · 2018Article
- Notch-1 Signaling Activation and Progesterone Receptor Expression in Ectopic Lesions of Women With Endometriosis.Journal of the Endocrine Society · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Interleukin-6 (IL-6) and Notch signaling are important regulators of breast cancer stem cells (CSCs), which drive the malignant phenotype through self-renewal, differentiation, and development of therapeutic resistance. We investigated the role of integrin-linked kinase (ILK) in regulating IL-6-driven Notch1 activation and the ability to target breast CSCs through ILK inhibition. Ectopic expression/short hairpin RNA-mediated knockdown of ILK, pharmacological inhibition of ILK with the small molecule T315, Western blot analysis, immunofluorescence, and luciferase reporter assays were used to evaluate the regulation of IL-6-driven Notch1 activation by ILK in IL-6-producing triple-negative breast cancer cell lines (MDA-MB-231, SUM-159) and in MCF-7 and MCF-7(IL-6) cells. The effects of ILK on γ-secretase complex assembly and cellular localization were determined by immunofluorescence, Western blots of membrane fractions, and immunoprecipitation. In vivo effects of T315-induced ILK inhibition on CSCs in SUM-159 xenograft models were assessed by mammosphere assays, flow cytometry, and tumorigenicity assays. Results show that the genetic knockdown or pharmacological inhibition of ILK suppressed Notch1 activation and the abundance of the γ-secretase components presenilin-1, nicastrin, and presenilin enhancer 2 at the posttranscriptional level via inhibition of caveolin-1-dependent membrane assembly of the γ-secretase complex. Accordingly, knockdown of ILK inhibited breast CSC-like properties in vitro and the breast CSC subpopulation in vivo in xenograft tumor models. Based on these findings, we propose a novel function of ILK in regulating γ-secretase-mediated Notch1 activation, which suggests the targeting of ILK as a therapeutic approach to suppress IL-6-induced breast CSCs.
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Registered trials
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.