Targeting the BDNF/TrkB pathway for the treatment of tumors (Review)

Meng, Lingbin; Liu, Baoqiong; Ji, Rui; Jiang, Xin; Yan, Xinfeng; Xin, Ying

doi:10.3892/ol.2018.9854

Cited by 65 publications

(88 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TrkB has been reported to regulate cellular proliferation in various cancer cells (reviewed in [12,27]). In accordance with this notion, TrkB knockdown in the SK-N-SH cell line in hypoxia caused inhibition of cellular proliferation in this study ( Figure 2I).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that TrkB activation initiates three downstream signaling cascades, namely PI3K/AKT/mTOR, Ras/extracellular signal-regulated kinase (ERK), and phospholipase C-γ/protein kinase C (PLCγ/PKC) [12,27]. The activating mutations of the K-ras gene constitutively turn on the downstream K-ras-transduced signaling pathways, Ras/ERK and PI3K/AKT.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Licochalcone A Inhibits BDNF and TrkB Gene Expression and Hypoxic Growth of Human Tumor Cell Lines

Arita

Koike

Yoshikawa³

et al. 2020

IJMS

View full text Add to dashboard Cite

Hypoxic cellular proliferation is a common feature of tumor cells and is associated with tumor progression. Therefore, the inhibition of hypoxic cellular proliferation is expected to regulate malignancy processes. Licochalcone A (LicA) is known to show inhibitory effects on cell growth in normoxia, but it is unclear whether LicA exerts similar effects in hypoxia. Here, we studied the inhibitory activity of LicA in the hypoxic cellular proliferation of tumor cells and its molecular mechanism using human cell lines derived from various tumors including neuroblastoma and colorectal cancer. LicA inhibited cell growth at a 50% inhibitory concentration between 7.0 and 31.1 µM in hypoxia. LicA significantly suppressed hypoxic induction of tropomyosin receptor kinase B (TrkB) gene expression at the transcription level. LicA also downregulated mRNA levels of the TrkB high-affinity ligand brain-derived neurotrophic factor, but not neurotrophin-4, another TrkB ligand, or glyceraldehyde-3-phosphate dehydrogenase, indicating that the inhibitory activity of LicA is selective. Since both LicA-treatment and TrkB-knockdown decreased activation of protein kinase B in hypoxia, LicA exerts its inhibitory effect against hypoxic cell growth through inhibition of the TrkB-AKT axis. These results suggest that LicA has therapeutic potential for malignant tumors including neuroblastoma and colorectal cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Licochalcone A Inhibits BDNF and TrkB Gene Expression and Hypoxic Growth of Human Tumor Cell Lines

Arita

Koike

Yoshikawa³

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…It exerts its effects on brain function, including neuroprotection, vascular remodelling, neurogenesis, neuronal survival, and neuroplasticity, following injury to brain cells, particularly after ischemic insults (Chao, 2003;Ohira and Hayashi, 2009;Lu et al, 2013). Additionally, BDNF regulates neuronal survival, cell migration, and synaptic function (Thoenen, 1995;Murer et al, 2001;Baydyuk and Xu, 2014;Lu et al, 2014;Meng et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of poly(lactic-co-glycolic acid) nanoparticle-bound brain-derived neurotrophic factor in a permanent middle cerebral artery occlusion model of ischemia in rats

Kamarudin¹,

Iezhitsa²,

Tripathy³

et al. 2020

Acta Neurobiologiae Experimentalis

View full text Add to dashboard Cite

Poly (lactide-co-glycolide) (PLGA) nanoparticles (NPs) are biodegradable carriers that participate in the transport of neuroprotective drugs across the blood brain barrier (BBB). Targeted brain-derived neurotrophic factor (BDNF) delivery across the BBB could provide neuroprotection in brain injury. We tested the neuroprotective effect of PLGA nanoparticle-bound BDNF in a permanent middle cerebral artery occlusion (pMCAO) model of ischemia in rats. Sprague-Dawley rats were subjected to pMCAO. Four hours after pMCAO, two groups were intravenously treated with BDNF and NP-BDNF, respectively. Functional outcome was assessed at 2 and 24 h after pMCAO, using the modified neurologic severity score (mNSS) and rotarod performance tests. Following functional assessments, rats were euthanized blood was taken to assess levels of the neurobiomarkers neuron-specific enolase and S100 calcium-binding protein β (S100β), and the brain was evaluated to measure the infarct volume. The NP-BDNF-treated group showed significant improvement in mNSS compared with pMCAO and BDNF-treated groups and showed improved rotarod performance. The infarct volume in rats treated with NP-BDNFs was also significantly smaller. These results were further corroborated by correlating differences in estimated NSE and S100β. NP-BDNFs exhibit a significant neuroprotective effect in the pMCAO model of ischemia in rats.

show abstract

“…NTRK2 was shown to serve as an oncogene in multiple cancers (19)(20)(21)(22), and its increased expression was associated with poor outcome (23,24). Based on this, inhibition of NTRK2-encoded TRKB was shown to induce antitumor effects and cellular apoptosis (25,26). Similar to NTRK1, NTRK3 has been demonstrated to be an oncogene in breast cancer and gastric cancer (27,28), but it acts as a tumor suppressor gene in CRC, neuroblastomas, and head and neck squamous cell carcinoma (10,29,30).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer

Chen

Huang

Luo

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Neurotrophic tropomyosin receptor kinases (NTRKs) are a gene family function as oncogene or tumor suppressor gene in distinct cancers. We aimed to investigate the methylation and expression profiles and prognostic value of NTRKs gene in colorectal cancer (CRC).Methods: An analysis of DNA methylation and expression profiles in CRC patients was performed to explore the critical methylations within NTRKs genes. The methylation marker was validated in a retrospectively collected cohort of 229 CRC patients and tested in other tumor types from TCGA. DNA methylation status was determined by quantitative methylation-specific PCR (QMSP).Results: The profiles in six CRC cohorts showed that NTRKs gene promoter was more frequently methylated in CRC compared to normal mucosa, which was associated with suppressed gene expression. We identified a specific methylated region within NTRK3 promoter targeted by cg27034819 and cg11525479 that best predicted survival outcome in CRC. NTRK3 promoter methylation showed independently predictive value for survival outcome in the validation cohort (P = 0.004, HR = 2.688, 95% CI = [1.355, 5.333]). Based on this, a nomogram predicting survival outcome was developed with a C-index of 0.705. Furthermore, the addition of NTRK3 promoter methylation improved the performance of currently-used prognostic model (AIC: 516.49 vs 513.91; LR: 39.06 vs 43.64, P = 0.032). Finally, NTRK3 promoter methylation also predicted survival in other tumors, including pancreatic cancer, glioblastoma and stomach adenocarcinoma.Conclusions: This study highlights the essential value of NTRK3 methylation to evaluate prognosis risk, improve current prognostic models and the potential to guide treatment in CRC and other tumors.

show abstract

Targeting the BDNF/TrkB pathway for the treatment of tumors (Review)

Cited by 65 publications

References 108 publications

Licochalcone A Inhibits BDNF and TrkB Gene Expression and Hypoxic Growth of Human Tumor Cell Lines

Licochalcone A Inhibits BDNF and TrkB Gene Expression and Hypoxic Growth of Human Tumor Cell Lines

Neuroprotective effect of poly(lactic-co-glycolic acid) nanoparticle-bound brain-derived neurotrophic factor in a permanent middle cerebral artery occlusion model of ischemia in rats

Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer

Contact Info

Product

Resources

About