ArticleOncogene2018
Neurotensin receptor type 2 protects B-cell chronic lymphocytic leukemia cells from apoptosis.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- SurvGRN: a multi-feature fusion framework for bladder cancer survival prediction.International journal of surgery (London, England) · 2026Article
- The Expression and Oncogenic Role of NTSR2 in Human Glioblastoma.OncoTargets and therapy · 2026Article
- Extracellular vesicles from type-2 macrophages increase the survival of chronic lymphocytic leukemia cells ex vivo.Cancer gene therapy · 2024Article
- Targeting the NTSR2/TrkB oncogenic pathway in chronic lymphocytic leukemia.Scientific reports · 2024Article
- miR-603 promotes cell proliferation and differentiation by targeting TrkB in acute promyelocytic leukemia.Annals of hematology · 2023Article
- The Role of the Microenvironment and Cell Adhesion Molecules in Chronic Lymphocytic Leukemia.Cancers · 2023Review
- Design, Synthesis, and Biological Evaluation of the First Radio-Metalated Neurotensin Analogue Targeting Neurotensin Receptor 2.ACS omega · 2023Article
- The genomic landscape of pediatric renal cell carcinomas.iScience · 2022Article
- Overexpression of sortilin is associated with 5-FU resistance and poor prognosis in colorectal cancer.Journal of cellular and molecular medicine · 2021Article
- Neurotensin pathway in digestive cancers and clinical applications: an overview.Cell death & disease · 2020Review
- Macrophage Polarization in Chronic Lymphocytic Leukemia: Nurse-Like Cells Are the Caretakers of Leukemic Cells.Biomedicines · 2020Review
- Upregulation ofInternational journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
B-cell chronic lymphocytic leukemia (B-CLL) cells are resistant to apoptosis, and consequently accumulate to the detriment of normal B cells and patient immunity. Because current therapies fail to eradicate these apoptosis-resistant cells, it is essential to identify alternative survival pathways as novel targets for anticancer therapies. Overexpression of cell-surface G protein-coupled receptors drives cell transformation, and thus plays a critical role in malignancies. In this study, we identified neurotensin receptor 2 (NTSR2) as an essential driver of apoptosis resistance in B-CLL. NTSR2 was highly expressed in B-CLL cells, whereas expression of its natural ligand, neurotensin (NTS), was minimal in both B-CLL cells and patient plasma. Surprisingly, NTSR2 remained in a constitutively active phosphorylated state, caused not by a mutation-induced gain-of-function but rather by an interaction with the oncogenic tyrosine kinase receptor TrkB. Functional and biochemical characterization revealed that the NTSR2-TrkB interaction acts as a conditional oncogenic driver requiring the TrkB ligand brain-derived neurotrophic factor (BDNF), which unlike NTS is highly expressed in B-CLL cells. Together, NTSR2, TrkB and BDNF induce autocrine and/or paracrine survival pathways that are independent of mutation status and indolent or progressive disease course. The NTSR2-TrkB interaction activates survival signaling pathways, including the Src and AKT kinase pathways, as well as expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL. When NTSR2 was downregulated, TrkB failed to protect B-CLL cells from a drastic decrease in viability via typical apoptotic cell death, reflected by DNA fragmentation and Annexin V presentation. Together, our findings demonstrate that the NTSR2-TrkB interaction plays a crucial role in B-CLL cell survival, suggesting that inhibition of NTSR2 represents a promising targeted strategy for treating B-CLL malignancy.
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