ArticleGastroenterology2015
Genomic instability causes HGF gene activation in colon cancer cells, promoting their resistance to necroptosis.
Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Hepatocyte growth factor is a prognostic marker in patients with colorectal cancer: a meta-analysis.Oncotarget · 2017Pooled it
- ETV4 Promotes Colorectal Cancer Progression by Reprogramming Asparagine Metabolism to Remodel the Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting cell death: a promising approach for colorectal cancer therapy.Cancer cell international · 2026Review
- A multiomics Mendelian randomization study on PANoptosis-related genes and gastric cancer risk.The Journal of international medical research · 2026Article
- MMP14-Dependent Activation of TGF-β Signaling Enhances Malignancies via Promoting Necroptosis in Glioblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Targeting the Met-RIPK1 signaling axis to enforce apoptosis and necroptosis in colorectal cancer.Cell death & disease · 2025Article
- Cascade loop of ferroptosis induction and immunotherapy based on metal-phenolic networks for combined therapy of colorectal cancer.Exploration (Beijing, China) · 2025Article
- Hepatocyte growth factor promotes melanoma metastasis through ubiquitin-specific peptidase 22-mediated integrins upregulation.Cancer letters · 2024Article
- PANoptosis-related genes function as efficient prognostic biomarkers in colon adenocarcinoma.Frontiers in endocrinology · 2024Article
- Identification of necroptosis-related lncRNAs for prognosis prediction and screening of potential drugs in patients with colorectal cancer.World journal of gastrointestinal oncology · 2023Article
- Understanding the Impact of Population and Cancer Type on Tumor Mutation Burden Scores: A Comprehensive Whole-Exome Study in Cancer Patients From India.JCO global oncology · 2023Article
- Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- An absolute approach to using whole exome DNA and RNA workflow for cancer biomarker testing.Frontiers in oncology · 2023Article
- Tyrosine phosphorylation regulates RIPK1 activity to limit cell death and inflammation.Nature communications · 2022Article
- Necroptosis pathways in tumorigenesis.Seminars in cancer biology · 2022Review
- Cetuximab resistance induced by hepatocyte growth factor is overcome by MET inhibition in KRAS, NRAS, and BRAF wild-type colorectal cancers.Journal of cancer research and clinical oncology · 2022Article
- Systems approaches to uncovering the contribution of environment-mediated drug resistance.Current opinion in solid state & materials science · 2022Article
- Non-Canonical Programmed Cell Death in Colon Cancer.Cancers · 2022Review
- Review
- Evoking Highly Immunogenic Ferroptosis Aided by Intramolecular Motion-Induced Photo-Hyperthermia for Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsGenomic instability promotes colon carcinogenesis by inducing genetic mutations, but not all genes affected by this process have been identified. We investigated whether genomic instability in human colorectal cancer (CRC) cells produces mutations in the hepatocyte growth factor (HGF) gene.
methodsWe genotyped human colon tumor tissues and adjacent nontumor tissues collected from 78 patients University of Pittsburgh Health Sciences and Veterans Hospital, along with 40 human CRC and adjacent nontumor tissues in a commercial microarray. We used cellular, biochemical, and molecular biological techniques to investigate the factors that alter HGF signaling in colon cancer cells and its effects on cell proliferation and survival.
resultsAll tested human CRC tissues and cell lines that had microsatellite instability contained truncations in the regulatory deoxyadenosine tract element (DATE) of the HGF gene promoter. The DATE was unstable in 14% (11 of 78) of CRC samples; DATE truncation was also polymorphic and detected in 18% (13 of 78) of CRC tissues without microsatellite instability. In CRC cell lines, truncation of DATE activated expression of HGF, resulting in its autocrine signaling via MET. This promoted cell proliferation and resistance to necroptosis. HGF signaling via MET reduced levels of the receptor-interacting serine-threonine kinase 1, a mediator of necroptosis, in CRC cells. High levels of HGF protein in tumor tissues correlated with lower levels of receptor-interacting serine-threonine kinase 1 and shorter survival times of patients.
conclusionsThirty-one percent of CRC samples contain alterations in the DATE of the HGF promoter. Disruption of the DATE increased HGF signaling via MET and reduced levels of receptor-interacting serine-threonine kinase 1 and CRC cell necroptosis. DATE alteration might be used as a prognostic factor or to select patients for therapies that target HGF-MET signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.