ArticleInternational journal of oncology2016
The hepatocyte growth factor antagonist NK4 inhibits indoleamine-2,3-dioxygenase expression via the c-Met-phosphatidylinositol 3-kinase-AKT signaling pathway.
Article in International journal of oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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
17 citing papers in PubMed, 23 citations in OpenAlex.
- Machine learning developed immune-related exosome signature for prognosis and immunotherapy benefit in bladder cancer.Discover oncology · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Overexpression of NK4 gene in TU212 affects migratory activity in laryngeal squamous cell carcinoma.Frontiers in oncology · 2025Article
- A Phase I Trial of the Dual MET Kinase/OCT-2 Inhibitor OMO-1 in Metastatic Solid Malignancies Including MET Exon 14 Mutated Lung Cancer.The oncologist · 2023Article
- Evolving therapeutic landscape of advanced hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2023Review
- Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise.World journal of hepatology · 2023Review
- Targeting micro-environmental pathways by PROTACs as a therapeutic strategy.Seminars in cancer biology · 2022Review
- Astragaloside IV Inhibits the Proliferation of Human Uterine Leiomyomas by Targeting IDO1.Cancers · 2022Article
- Targeting the cMET pathway to enhance immunotherapeutic approaches for mUM patients.Frontiers in oncology · 2022Review
- Indoleamine 2,3-Dioxygenase Activity-Induced Acceleration of Tumor Growth, and Protein Kinases-Related Novel Therapeutics Regimens.Advances in experimental medicine and biology · 2021Article
- Molecular phenotypes of circulating tumor cells and efficacy of nivolumab treatment in patients with head and neck squamous cell carcinoma.Scientific reports · 2020Article
- Is there any place for immune-checkpoint inhibitors in the treatment algorithm of fusion-driven non-small cell lung cancer?-a literature review.Translational lung cancer research · 2020Review
- Preparation, Characterization, and in vivo Evaluation of NK4-Conjugated Hydroxycamptothecin-Loaded Liposomes.International journal of nanomedicine · 2020Article
- The Emerging Role of the c-MET-HGF Axis in Non-small Cell Lung Cancer Tumor Immunology and Immunotherapy.Frontiers in oncology · 2020Review
- Detection of HIV-1 and Human Proteins in Urinary Extracellular Vesicles from HIV+ Patients.Advances in virology · 2018Article
- How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair.Molecules (Basel, Switzerland) · 2017Review
- New Therapeutic Options for Advanced Hepatocellular Carcinoma.Cancer control : journal of the Moffitt Cancer CenterArticle
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 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Indoleamine-2,3-dioxygenase (IDO) is an immunosuppressive enzyme involved in tumor malignancy. However, the regulatory mechanism underlying its involvement remains largely uncharacterized. The present study aimed to investigate the hypothesis that NK4, an antagonist of hepatocyte growth factor (HGF), can regulate IDO and to characterize the signaling mechanism involved. Following successful transfection of the human ovarian cancer cell line SKOV-3 (which constitutively expresses IDO) with an NK4 expression vector, we observed that NK4 expression suppressed IDO expression; furthermore, NK4 expression did not suppress cancer cell growth in vitro [in the absence of natural killer (NK) cells], but did influence tumor growth in vivo. In addition, NK4 enhanced the sensitivity of cancer cells to NK cells in vitro and promoted NK cell accumulation in the tumor stroma in vivo. In an effort to clarify the mechanisms by which NK4 interacts with IDO, we performed investigations utilizing various biochemical inhibitors. The results of these investigations were as follows. First, c-Met (a receptor of HGF) tyrosine kinase inhibitor PHA-665752, and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 both suppress IDO expression. Second, enhanced expression of PTEN (a known tumor suppressor) via negative regulation within a PI3K-AKT pathway, inhibits IDO expression. Conversely, neither the MEK1/2 inhibitor U0126 nor the STAT3 inhibitor WP1066 affects IDO expression. These results suggest that NK4 inhibits IDO expression via a c-Met-PI3K-AKT signaling pathway.
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.