ArticleOncogene2011
ATM-dependent IGF-1 induction regulates secretory clusterin expression after DNA damage and in genetic instability.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Review
- Review
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- Clusterin Expression in Colorectal Carcinomas.International journal of molecular sciences · 2023Review
- BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling.Nature communications · 2022Article
- Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers.Frontiers in cell and developmental biology · 2021Review
- Depletion of insulin-like growth factor 1 receptor increases radiosensitivity in colorectal cancer.Journal of gastrointestinal oncology · 2020Article
- Peptide Hormone Regulation of DNA Damage Responses.Endocrine reviews · 2020Review
- The role of Clusterin in cancer metastasis.Cancer management and research · 2019Article
- Clusterin increases mitochondrial respiratory chain complex I activity and protects against hexavalent chromium-induced cytotoxicity in L-02 hepatocytes.Toxicology research · 2019Article
- The IGF-1R/AKT pathway has opposing effects on Nutlin-3a-induced apoptosis.Cancer biology & therapy · 2017Article
- Manganese and the Insulin-IGF Signaling Network in Huntington's Disease and Other Neurodegenerative Disorders.Advances in neurobiology · 2017Review
- The IGF-1R/AKT pathway determines cell fate in response to p53.Translational cancer research · 2016Article
- IGF-1R inhibition sensitizes breast cancer cells to ATM-related kinase (ATR) inhibitor and cisplatin.Oncotarget · 2016Article
- Article
- Clusterin, a gene enriched in intestinal stem cells, is required for L1-mediated colon cancer metastasis.Oncotarget · 2015Article
- HMGB1 induction of clusterin creates a chemoresistant niche in human prostate tumor cells.Scientific reports · 2015Article
- Article
- IGF1 stimulates crypt expansion via differential activation of 2 intestinal stem cell populations.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Clusterin facilitates metastasis by EIF3I/Akt/MMP13 signaling in hepatocellular carcinoma.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Secretory clusterin (sCLU) is a stress-induced, pro-survival glycoprotein elevated in early-stage cancers, in particular in APC/Min-defective colon cancers. sCLU is upregulated after exposure to various cytotoxic agents, including ionizing radiation (IR), leading to a survival advantage. We found that stimulation of insulin-like growth factor-1 (IGF-1) and IGF-1R protein kinase signaling was required for sCLU induction after IR exposure. Here, we show that activation of Ataxia telangiectasia-mutated kinase (ATM) by endogenous or exogenous forms of DNA damage was required to relieve basal repression of IGF-1 transcription by the p53/NF-YA complex, leading to sCLU expression. Although p53 levels were stabilized and elevated after DNA damage, dissociation of NF-YA, and thereby p53, from the IGF-1 promoter resulted in IGF-1 induction, indicating that NF-YA was rate limiting. Cells with elevated endogenous DNA damage (deficient in H2AX, MDC1, NBS1, mTR or hMLH1) or cells exposed to DNA-damaging agents had elevated IGF-1 expression, resulting in activation of IGF-1R signaling and sCLU induction. In contrast, ATM-deficient cells were unable to induce sCLU after DNA damage. Our results integrate DNA damage resulting from genetic instability, IR, or chemotherapeutic agents, to ATM activation and abrogation of p53/NF-YA-mediated IGF-1 transcriptional repression, that induces IGF-1-sCLU expression. Elucidation of this pathway should uncover new mechanisms for cancer progression and reveal new targets for drug development to overcome resistance to therapy.
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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.