ArticlePloS one2012
A novel role for BDNF-TrkB in the regulation of chemotherapy resistance in head and neck squamous cell carcinoma.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
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- The Role of the Neurotrophin Network in Skin Squamous Cell Cancer and the Novel Use of the Zebrafish System.JID innovations : skin science from molecules to population health · 2024Review
- Effect of BIM expression on the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs.Scientific reports · 2023Article
- Influence of EGF and pro-NGF on EGFR/SORTILIN interaction and clinical impact in head and neck squamous cell carcinoma.Frontiers in oncology · 2023Article
- Oncogenic role of a developmentally regulatedScience advances · 2022Article
- Interactions Among Brain-Derived Neurotrophic Factor and Neuroimmune Pathways Are Key Components of the Major Psychiatric Disorders.Molecular neurobiology · 2022Review
- Article
- Identification of a Novel Five-Gene Signature as a Prognostic and Diagnostic Biomarker in Colorectal Cancers.International journal of molecular sciences · 2022Article
- Treatment effects of the EGFR pathway drugs on head and neck cancer stem cells.American journal of cancer research · 2022Article
- Isolation and characterization of head and neck cancer-derived peritumoral and cancer-associated fibroblasts.Frontiers in oncology · 2022Article
- proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model.Translational psychiatry · 2021Article
- Anti-EGFR treatment effects on laryngeal cancer stem cells.American journal of translational research · 2021Article
- TrkB-Targeted Therapy for Mucoepidermoid Carcinoma.Biomedicines · 2020Article
- Do DLX3 and CD271 Protect Human Keratinocytes from Squamous Tumor Development?International journal of molecular sciences · 2019Article
- Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection.Cancer research and treatment · 2019Article
- Identification of exosomal and non‑exosomal microRNAs associated with the drug resistance of ovarian cancer.Molecular medicine reports · 2019Article
- Targeting the BDNF/TrkB pathway for the treatment of tumors.Oncology letters · 2019Review
- Brain-Derived Neurotrophin and TrkB in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2019Article
- TRKB tyrosine kinase receptor is a potential therapeutic target for poorly differentiated oral squamous cell carcinoma.Oncotarget · 2018Article
- Identification of genes and pathways associated with MDR in MCF-7/MDR breast cancer cells by RNA-seq analysis.Molecular medicine reports · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mechanisms of resistance for HNSCC to cisplatin (CDDP), the foundational chemotherapeutic agent in the treatment of this disease, remain poorly understood. We previously demonstrated that cisplatin resistance (CR) can be overcome by targeting Trk receptor. In the current study, we explored the potential mechanistic role of the BDNF-TrkB signaling system in the development of CDDP resistance in HNSCC. Utilizing an in vitro system of acquired CR, we confirmed a substantial up-regulation of both BDNF and TrkB at the protein and mRNA levels in CR cells, suggesting an autocrine pathway dysregulation in this system. Exogenous BDNF stimulation led to an enhanced expression of the drug-resistance and anti-apoptotic proteins MDR1 and XiAP, respectively, in a dose-dependently manner, demonstrating a key role for BDNF-TrkB signaling in modulating the response to cytotoxic agents. In addition, modulation of TrkB expression induced an enhanced sensitivity of cells to CDDP in HNSCC. Moreover, genetic suppression of TrkB resulted in changes in expression of Bim, XiAP, and MDR1 contributing to HNSCC survival. To elucidate intracellular signaling pathways responsible for mechanisms underlying BDNF/TrkB induced CDDP-resistance, we analyzed expression levels of these molecules following inhibition of Akt. Inhibition of Akt eliminated BDNF effect on MDR1 and Bim expression in OSC-19P cells as well as modulated expressions of MDR1, Bim, and XiAP in OSC-19CR cells. These results suggest BDNF/TrkB system plays critical roles in CDDP-resistance development by utilizing Akt-dependent signaling pathways.
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