ArticleOncotarget2016
NTS/NTR1 co-expression enhances epithelial-to-mesenchymal transition and promotes tumor metastasis by activating the Wnt/β-catenin signaling pathway in hepatocellular carcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Cardiometabolic risk factors in MASLD patients with HCC: the other side of the coin.Frontiers in endocrinology · 2024Review
- Review
- Article
- Expression of neurotensin receptor-1 (NTSBreast cancer research and treatment · 2021Article
- Article
- Overexpressed sFRP3 exerts an inhibitory effect on hepatocellular carcinoma via inactivation of the Wnt/β-catenin signaling pathway.Cancer gene therapy · 2021Article
- Klotho Inhibits Proliferation in a RET Fusion Model of Papillary Thyroid Cancer by Regulating the Wnt/β-Catenin Pathway.Cancer management and research · 2021Article
- An Immune-Related Signature Predicted Survival in Patients With Kidney Papillary Cell Carcinoma.Frontiers in oncology · 2021Article
- Neurotensin pathway in digestive cancers and clinical applications: an overview.Cell death & disease · 2020Review
- The role of Neurotensin and its receptors in non-gastrointestinal cancers: a review.Cell communication and signaling : CCS · 2020Review
- Total flavonoids suppress lung cancer growth via the COX-2-mediated Wnt/β-catenin signaling pathway.Oncology letters · 2020Article
- Down-Regulated CMTM2 Promotes Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.OncoTargets and therapy · 2020Article
- Neurotensin receptors regulate transactivation of the EGFR and HER2 in a reactive oxygen species-dependent manner.European journal of pharmacology · 2019Article
- Screening and identification of biomarkers associated with clinicopathological parameters and prognosis in oral squamous cell carcinoma.Experimental and therapeutic medicine · 2019Article
- Neurotensin Receptor-1 Expression in Human Prostate Cancer: A Pilot Study on Primary Tumors and Lymph Node Metastases.International journal of molecular sciences · 2019Article
- Overexpression of HDAC6 suppresses tumor cell proliferation and metastasis by inhibition of the canonical Wnt/β-catenin signaling pathway in hepatocellular carcinoma.Oncology letters · 2018Article
- DDX39 promotes hepatocellular carcinoma growth and metastasis through activating Wnt/β-catenin pathway.Cell death & disease · 2018Article
- Benzo(a)pyrene promotes Hep-G2 cell migration and invasion by upregulating phosphorylated extracellular signal-regulated kinase expression.Oncology letters · 2018Article
- Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurotensin (NTS) is a neuropeptide distributed in central nervous and digestive systems. In this study, the significant association between ectopic NTS expression and tumor invasion was confirmed in hepatocellular carcinoma (HCC). In primary HCC tissues, the NTS and neurotensin receptor 1 (NTR1) co-expression (NTS+NTR1+) is a poor prognostic factor correlated with aggressive biological behaviors and poor clinical prognosis. Enhanced epithelial-to-mesenchymal transition (EMT) features, including decreased E-cadherin, increased β-catenin translocation and N-cadherin expression, were identified in NTS+NTR1+ HCC tissues. Varied NTS-responsible HCC cell lines were established using NTR1 genetically modified Hep3B and HepG2 cells which were used to elucidate the molecular mechanisms regulating NTS-induced EMT and tumor invasion in vitro. Results revealed that inducing exogenous NTS stimulation and enhancing NTR1 expression promoted tumor invasion rather than proliferation by accelerating EMT in HCC cells. The NTS-induced EMT was correlated with the remarkable increase in Wnt1, Wnt3, Wnt5, Axin, and p-GSK3β expression and was significantly reversed by blocking the NTS signaling via the NTR1 antagonist SR48692 or by inhibiting the activation of the Wnt/β-catenin pathway via specific inhibitors, such as TSW119 and DKK-1. SR48692 also inhibited the metastases of NTR1-overexpressing HCC xenografts in the lungs in vivo. This finding implied that NTS may be an important stimulus to promote HCC invasion and metastasis both in vitro and in vivo, and NTS signaling enhanced the tumor EMT and invasion potentials by activating the canonical Wnt/β-catenin signaling pathway. Therefore, NTS may be a valuable therapeutic target to prevent tumor progression in HCC.
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