ArticleOncotarget2014
Activation of EGFR, HER2 and HER3 by neurotensin/neurotensin receptor 1 renders breast tumors aggressive yet highly responsive to lapatinib and metformin in mice.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Obesity-related gut hormones and cancer: novel insight into the pathophysiology.International journal of obesity (2005) · 2021Pooled it
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- Targeting oncogenic NTSR1 with liensinine reprograms Gq-mediated signaling to suppress lung adenocarcinoma.Chinese medicine · 2026Article
- Review
- Article
- Radiocobalt theranostic applications: current landscape, challenges, and future directions.Frontiers in nuclear medicine · 2025Review
- Neurotensin and Its Involvement in Female Hormone-Sensitive Cancers.International journal of molecular sciences · 2024Review
- NTSR1 glycosylation and MMP dependent cleavage generate three distinct forms of the protein.Scientific reports · 2023Article
- Adding of neurotensin to non-small cell lung cancer cells increases tyrosine phosphorylation of HER3.Peptides · 2022Article
- Supply chain logistics - the role of the Golgi complex in extracellular matrix production and maintenance.Journal of cell science · 2022Review
- Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer.Nature communications · 2021Article
- Neurotensin: A novel mediator of ovulation?FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The role of Neurotensin and its receptors in non-gastrointestinal cancers: a review.Cell communication and signaling : CCS · 2020Review
- Neuropeptide bombesin receptor activation stimulates growth of lung cancer cells through HER3 with a MAPK-dependent mechanism.Biochimica et biophysica acta. Molecular cell research · 2020Article
- Validation of Neurotensin Receptor 1 as a Therapeutic Target for Gastric Cancer.Molecules and cells · 2018Article
- Advances in studies of tyrosine kinase inhibitors and their acquired resistance.Molecular cancer · 2018Review
- Neurotensin receptor type 2 protects B-cell chronic lymphocytic leukemia cells from apoptosis.Oncogene · 2018Article
- Review
- Expression of neurotensin receptor 1 in endometrial adenocarcinoma is correlated with histological grade and clinical outcome.Virchows Archiv : an international journal of pathology · 2017Article
- Improved anticancer drug response prediction in cell lines using matrix factorization with similarity regularization.BMC cancer · 2017Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A present challenge in breast oncology research is to identify therapeutical targets which could impact tumor progression. Neurotensin (NTS) and its high affinity receptor (NTSR1) are up regulated in 20% of breast cancers, and NTSR1 overexpression was shown to predict a poor prognosis for 5 year overall survival in invasive breast carcinomas. Interactions between NTS and NTSR1 induce pro-oncogenic biological effects associated with neoplastic processes and tumor progression. Here, we depict the cellular mechanisms activated by NTS, and contributing to breast cancer cell aggressiveness. We show that neurotensin (NTS) and its high affinity receptor (NTSR1) contribute to the enhancement of experimental tumor growth and metastasis emergence in an experimental mice model. This effect ensued following EGFR, HER2, and HER3 over-expression and autocrine activation and was associated with an increase of metalloproteinase MMP9, HB-EGF and Neuregulin 2 in the culture media. EGFR over expression ensued in a more intense response to EGF on cellular migration and invasion. Accordingly, lapatinib, an EGFR/HER2 tyrosine kinase inhibitor, as well as metformin, reduced the tumor growth of cells overexpressing NTS and NTSR1. All cellular effects, such as adherence, migration, invasion, altered by NTS/NTSR1 were abolished by a specific NTSR1 antagonist. A strong statistical correlation between NTS-NTSR1-and HER3 (p< 0.0001) as well as NTS-NTSR1-and HER3- HER2 (p< 0.001) expression was found in human breast tumors. Expression of NTS/NTSR1 on breast tumoral cells creates a cellular context associated with cancer aggressiveness by enhancing epidermal growth factor receptor activity. We propose the use of labeled NTS/NTSR1 complexes to enlarge the population eligible for therapy targeting HERs tyrosine kinase inhibitor or HER2 overexpression.
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