ArticleInvestigational new drugs2012
K252a induces anoikis-sensitization with suppression of cellular migration in Epstein-Barr virus (EBV)--associated nasopharyngeal carcinoma cells.
Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 41 citations in OpenAlex.
- Lactoferrin inhibits anoikis-resistance and metastasis of nasopharyngeal carcinoma cells via the AKT signaling pathway.International journal of clinical and experimental pathology · 2026Article
- An integrative analysis combining bioinformatics, network pharmacology and experimental methods identified key genes of EGCG targets in Nasopharyngeal Carcinoma.Discover oncology · 2025Article
- Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets.Journal of hematology & oncology · 2022Review
- Unraveling the links between neurodegeneration and Epstein-Barr virus-mediated cell cycle dysregulation.Current research in neurobiology · 2022Review
- LMP1 promotes nasopharyngeal carcinoma metastasis through NTRK2-mediated anoikis resistance.American journal of cancer research · 2020Article
- Inhibin B suppresses anoikis resistance and migration through the transforming growth factor-β signaling pathway in nasopharyngeal carcinoma.Cancer science · 2018Article
- Proliferative role of BDNF/TrkB signaling is associated with anoikis resistance in cervical cancer.Oncology reports · 2018Article
- Nerve Growth Factor (NGF)-Receptor Survival Axis in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2018Article
- Modeling nasopharyngeal carcinoma in three dimensions.Oncology letters · 2017Article
- Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model.Cancer letters · 2016Article
- Anoikis and EMT: Lethal "Liaisons" during Cancer Progression.Critical reviews in oncogenesis · 2016Review
- TrkB inhibition by GNF-4256 slows growth and enhances chemotherapeutic efficacy in neuroblastoma xenografts.Cancer chemotherapy and pharmacology · 2015Article
- Uncovering a key to the process of metastasis in human cancers: a review of critical regulators of anoikis.Journal of cancer research and clinical oncology · 2013Review
- TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders.International journal of molecular sciences · 2013Review
- Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer.British journal of cancer · 2013Article
- Novel anti-cancer compounds for developing combinatorial therapies to target anoikis-resistant tumors.Pharmaceutical research · 2012Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies revealed an unexpected role of the neurotrophin receptor pathway, BDNF/TrkB signaling, in cancer metastasis and anoikis (i.e. detachment-induced cell death). Survival of cancer cells in detached state (known as anoikis-resistance) is known to be pre-requisite for metastasis. Nasopharyngeal carcinoma (NPC), an endemic head and neck cancer in Southeast Asia, is highly invasive, metastatic, and etiologically associated with Epstein-Barr virus (EBV, an oncovirus) infection. Mechanistic studies on the invasive/metastatic nature of NPC can facilitate the development of anti-metastatic therapy in NPC. Thus far, the role of BDNF/TrkB signaling in virus-associated human cancer is unclear. Here, using multiple cell line models of NPC with EBV-association (HONE-1-EBV, HK1-LMP1 and C666-1), we investigated the potential involvement of BDNF/TrkB signaling in cellular migration and anoikis-resistant characteristics of NPC. We found that all three EBV-associated NPC cell lines tested were intrinsically anoikis-resistant (i.e. survived in detached state) and expressed both BDNF and TrkB. BDNF stimulation induced cellular migration, but not proliferation of these cells. Further, we examined if pharmacologic targeting of anoikis-resistance of NPC cells can be achievable by a proof-of-concept Trk inhibitor, K252a, in these EBV-associated NPC models. Our results demonstrated that K252a, was able to attenuate BDNF-induced migration and proliferation of NPC cells. More importantly, we demonstrated for the first time that K252a harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced cell death) against EBV-associated human cancer cells, namely NPC cells. This proof-of-concept study demonstrated that K252a, a Trk inhibitor, can potentially be used as an anoikis-sensitizing agent in NPC.
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