ArticleOncogene2010
Suppression of Her2/neu expression through ILK inhibition is regulated by a pathway involving TWIST and YB-1.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Integrin-linked kinase (ILK) in hematologic malignancies: Bridging molecular mechanisms to therapeutic innovation.BioImpacts : BI · 2026Review
- Role of microRNA-363 during tumor progression and invasion.Journal of physiology and biochemistry · 2024Review
- Stress Granules Involved in Formation, Progression and Metastasis of Cancer: A Scoping Review.Frontiers in cell and developmental biology · 2021Article
- Stress Granules in the Anti-Cancer Medications Mechanism of Action: A Systematic Scoping Review.Frontiers in oncology · 2021Article
- The focal adhesion protein Integrin-Linked Kinase (ILK) as an important player in breast cancer pathogenesis.Cell adhesion & migration · 2020Review
- Long non-coding RNA SNHG5 affects the invasion and apoptosis of renal cell carcinoma by regulating the miR-363-3p-Twist1 interaction.American journal of translational research · 2020Article
- E2F1: Cause and Consequence of DNA Replication Stress.Frontiers in molecular biosciences · 2020Review
- Interaction network analysis of YBX1 for identification of therapeutic targets in adenocarcinomas.Journal of biosciences · 2019Article
- Targeting integrin-linked kinase to suppress oncogenic KRAS signaling in pancreatic cancer.Small GTPases · 2018Article
- Expression and network analysis of YBX1 interactors for identification of new drug targets in lung adenocarcinoma.Journal of genomics · 2018Article
- Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells.Oncotarget · 2016Article
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- Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer.Carcinogenesis · 2016Article
- Using Pharmacokinetic Profiles and Digital Quantification of Stained Tissue Microarrays as a Medium-Throughput, Quantitative Method for Measuring the Kinetics of Early Signaling Changes Following Integrin-Linked Kinase Inhibition in an In Vivo Model of Cancer.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2015Article
- 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.Neoplasia (New York, N.Y.) · 2015Article
- Inhibition of the HER2-YB1-AR axis with Lapatinib synergistically enhances Enzalutamide anti-tumor efficacy in castration resistant prostate cancer.Oncotarget · 2015Article
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- Integrin-linked kinase links dynactin-1/dynactin-2 with cortical integrin receptors to orient the mitotic spindle relative to the substratum.Scientific reports · 2015Article
- Tamoxifen inhibits ER-negative breast cancer cell invasion and metastasis by accelerating Twist1 degradation.International journal of biological sciences · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In a previous study it was found that the therapeutic effects of QLT0267, a small molecule inhibitor of integrin-linked kinase (ILK), were influenced by Her2/neu expression. To understand how inhibition or silencing of ILK influences Her2/neu expression, Her2/neu signaling was evaluated in six Her2/neu-positive breast cancer cell lines (LCC6(Her2), MCF7(Her2), SKBR3, BT474, JIMT-1 and KPL-4). Treatment with QLT0267 engendered suppression (32-87%) of total Her2/neu protein in these cells. Suppression of Her2/neu was also observed following small interfering RNA-mediated silencing of ILK expression. Time course studies suggest that ILK inhibition or silencing caused transient decreases in P-AKT(ser473), which were not temporally related to Her2/neu downregulation. Attenuation of ILK activity or expression was, however, associated with decreases in YB-1 (Y-box binding protein-1) protein and transcript levels. YB-1 is a known transcriptional regulator of Her2/neu expression, and in this study it is demonstrated that inhibition of ILK activity using QLT0267 decreased YB-1 promoter activity by 50.6%. ILK inhibition was associated with changes in YB-1 localization, as reflected by localization of cytoplasmic YB-1 into stress granules. ILK inhibition also suppressed TWIST (a regulator of YB-1 expression) protein expression. To confirm the role of ILK on YB-1 and TWIST, cells were engineered to overexpress ILK. This was associated with a fourfold increase in the level of YB-1 in the nucleus, and a 2- and 1.5-fold increase in TWIST and Her2/neu protein levels, respectively. Taken together, these data indicate that ILK regulates the expression of Her2/neu through TWIST and YB-1, lending support to the use of ILK inhibitors in the treatment of aggressive Her2/neu-positive tumors.
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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.