ArticleProceedings of the National Academy of Sciences of the United States of America2000
Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers, 1 of them a synthesis that pooled it.
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164 citing papers in PubMed, 1 synthesis or guideline pooled it, 432 citations in OpenAlex.
- Transcriptomic analysis of castration, chemo-resistant and metastatic prostate cancer elucidates complex genetic crosstalk leading to disease progression.Functional & integrative genomics · 2021Pooled it
- Integrin-Linked Kinase Suppression Reduces SPARC's Effect on Intraocular Pressure and Extracellular Matrix.Investigative ophthalmology & visual science · 2026Article
- 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
- The ILK-PINCH-parvin complex: a conserved primary adhesome regulating biological processes.Histochemistry and cell biology · 2025Review
- Integrin linked kinase and threonine tyrosine kinase modulate TCR signaling.Scientific reports · 2025Article
- Bioinformatics analysis combined with experimental validation reveals the biological role of the ILK gene in prostate cancer.Discover oncology · 2025Article
- Engineered Cardiac Tissues as a Platform for CRISPR-Based Mitogen Discovery.Advanced healthcare materials · 2025Article
- Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.Cancer metastasis reviews · 2024Review
- Synthetic rescue of Xeroderma Pigmentosum C phenotype via PIK3C3 downregulation.Cell death & disease · 2024Article
- WISP-1 Regulates Cardiac Fibrosis by Promoting Cardiac Fibroblasts' Activation and Collagen Processing.Cells · 2024Article
- Kinase-impaired BTK mutations are susceptible to clinical-stage BTK and IKZF1/3 degrader NX-2127.Science (New York, N.Y.) · 2024Article
- Article
- Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway.Zoological research · 2023Article
- Regulation of Kinase Signaling Pathways by α6β4-Integrins and Plectin in Prostate Cancer.Cancers · 2022Review
- Single-cell transcriptome analysis of regenerating RGCs reveals potent glaucoma neural repair genes.Neuron · 2022Article
- The kinase activity of integrin-linked kinase regulates cellular senescence in gastric cancer.Cell death & disease · 2022Article
- Article
- The Potential Tumor-Suppressor DHRS7 Inversely Correlates with EGFR Expression in Prostate Cancer Cells and Tumor Samples.Cancers · 2022Article
- Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes.Biomedicines · 2022Article
- Integrin-linked kinase (ILK): the known vs. the unknown and perspectives.Cellular and molecular life sciences : CMLS · 2022Review
104 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PTEN is a tumor suppressor gene located on chromosome 10q23 that encodes a protein and phospholipid phosphatase. Somatic mutations of PTEN are found in a number of human malignancies, and loss of expression, or mutational inactivation of PTEN, leads to the constitutive activation of protein kinase B (PKB)/Akt via enhanced phosphorylation of Thr-308 and Ser-473. We recently have demonstrated that the integrin-linked kinase (ILK) can phosphorylate PKB/Akt on Ser-473 in a phosphoinositide phospholipid-dependent manner. We now demonstrate that the activity of ILK is constitutively elevated in a serum- and anchorage-independent manner in PTEN-mutant cells, and transfection of wild-type (WT) PTEN into these cells inhibits ILK activity. Transfection of a kinase-deficient, dominant-negative form of ILK or exposure to a small molecule ILK inhibitor suppresses the constitutive phosphorylation of PKB/Akt on Ser-473, but not on Thr-308, in the PTEN-mutant prostate carcinoma cell lines PC-3 and LNCaP. Transfection of dominant-negative ILK and WT PTEN into these cells also results in the inhibition of PKB/Akt kinase activity. Furthermore, dominant-negative ILK or WT PTEN induces G(1) phase cycle arrest and enhanced apoptosis. Together, these data demonstrate a critical role for ILK in PTEN-dependent cell cycle regulation and survival and indicate that inhibition of ILK may be of significant value in PTEN-mutant tumor therapy.
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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.