ArticleCell death & disease2017
Smad7 knockdown activates protein kinase RNA-associated eIF2α pathway leading to colon cancer cell death.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Importance of PERK pathway modulation on colorectal cancer management: a systematic review.BMC cancer · 2025Pooled it
- A Pharmacological Batch of Mongersen that Downregulates Smad7 is Effective as Induction Therapy in Active Crohn's Disease: A Phase II, Open-Label Study.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Trial
- SMAD7-Associated Glycolytic Regulation Promotes Lactate-Dependent Macrophage Phenotype Modulation in Colorectal Cancer.Cancers · 2026Article
- Smad7 is a negative regulator of immunogenic cell death in colorectal cancer.Oncoimmunology · 2025Article
- Identification and characterization of colorectal-cancer-associated SNPs on the SMAD7 locus.Journal of cancer research and clinical oncology · 2023Article
- Article
- Knock-Out of the Five Lysyl-Oxidase Family Genes Enables Identification of Lysyl-Oxidase Pro-Enzyme Regulated Genes.International journal of molecular sciences · 2022Article
- Systematic Identification of Genomic Markers for Guiding Iron Oxide Nanoparticles in Cervical Cancer Based on Translational Bioinformatics.International journal of nanomedicine · 2022Article
- Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer.International journal of molecular sciences · 2021Review
- Role of TGF-Beta and Smad7 in Gut Inflammation, Fibrosis and Cancer.Biomolecules · 2020Review
- Targeting Protein Synthesis in Colorectal Cancer.Cancers · 2020Review
- Long non‑coding RNA LINC00858 promotes TP53‑wild‑type colorectal cancer progression by regulating the microRNA‑25‑3p/SMAD7 axis.Oncology reports · 2020Article
- MicroRNA-181c Suppresses the Biological Progression of Osteosarcoma via Targeting SMAD7 and Regulating Transforming Growth Factor-β (TGF-β) Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Review
- miR-181b-induced SMAD7 downregulation controls granulosa cell apoptosis through TGF-β signaling by interacting with the TGFBR1 promoter.Journal of cellular physiology · 2018Article
- Review
- Transforming Growth Factor-β1/Smad7 in Intestinal Immunity, Inflammation, and Cancer.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upregulation of Smad7, an inhibitor of transforming growth factor-β1 (TGF-β1), occurs in sporadic colorectal cancer (CRC) and knockdown of Smad7 inhibits CRC cell growth, a phenomenon that associates with decreased expression of cell division cycle 25 homolog A and arrest of cells in the S phase of the cell cycle. These findings occur in CRC cells unresponsive to TGF-β1, thus suggesting the existence of a Smad7-mediated TGF-β1-independent mechanism that controls CRC cell behavior. Here we show that Smad7 inhibition with a specific Smad7 antisense oligonucleotide upregulates eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, a transcription factor involved in the regulation of cell cycle arrest and induction of cell death, and induces activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homology protein (CHOP), two downstream targets of eIF2α. Among the upstream kinases that control eIF2α phosphorylation, the serine-threonine protein kinase RNA (PKR), but not general control non-derepressible 2 (GCN2) and protein kinase RNA-like endoplasmic reticulum kinase (PERK), is activated by Smad7 knockdown. PKR silencing abolishes Smad7 antisense-induced eIF2α phosphorylation and ATF4/CHOP induction, thereby preventing Smad7 antisense-driven cell death. Smad7 inhibition diminishes interaction of PKR with protein kinase inhibitor p58 (p58
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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.