Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer

Okamura, Kyoko; Harada, Taishi; Wang, Shuo; Ijichi, Kayo; Furuyama, Kazuto; Koga, Tomohiro; Okamoto, Tatsuro; Takayama, K.; Yano, Tokujiro; Nakanishi, Yoichi

doi:10.1016/j.lungcan.2012.07.011

Cited by 89 publications

(85 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BDNF/TrkB overexpression (Table i) confers a migratory phenotype to tumor cells and primes cancer cells to resist substantial genotoxic stressors, most of which are front-line chemotherapies (4-6). BDNF-mediated activation of TrkB also results in RAs activation (7), in turn accelerating cell-cycle progression and presumably contributing to poor prognosis of patients with cancers dependent on the BDNF signaling pathway (8,9). BDNF and Trkb overexpression has also been shown to contribute to oncogenesis of aggressive neuroblastoma cells (10) and to post-chemotherapeutic recurrence of highly aggressive breast cancer stem cells (11), demonstrating that this signaling pathway seems to be ubiquitous in the progression of multiple cancers and dynamically regulates several aspects of tumor cell physiology.…”

Section: Abstract Neurotrophins Are a Family Of Growth Factors That mentioning

confidence: 99%

BDNF: An Oncogene or Tumor Suppressor?

Radin

Patel

2017

View full text Add to dashboard Cite

Section: Abstract Neurotrophins Are a Family Of Growth Factors That mentioning

confidence: 99%

BDNF: An Oncogene or Tumor Suppressor?

Radin

Patel

2017

View full text Add to dashboard Cite

“…It involves in a variety of neural and molecular events and plays an important role in both brain development and synaptic plasticity (Hong et al 2011). Recently, BDNF has been reported to be associated with tumor progression in several human malignancies, such as neuroblastoma (Czarnecka et al 2014), lung cancer (Okamura et al 2012), breast cancer, and colon cancer (Yang et al 2012(Yang et al , 2013. BDNF and its receptor, TrkB, are commonly upregulated in a variety of human tumors (Guo et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Brain-derived neurotrophic factor regulates cell motility in human colon cancer

Huang¹,

Lin²,

Lin³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to affect cancer cell metastasis and migration. In the present study, we investigated the mechanisms of BDNF-induced cell migration in colon cancer cells. The migratory activities of two colon cancer cell lines, HCT116 and SW480, were found to be increased in the presence of human BDNF. Heme oxygenase-1 (HO)-1 is known to be involved in the development and progression of tumors. However, the molecular mechanisms that underlie HO-1 in the regulation of colon cancer cell migration remain unclear. Expression of HO-1 protein and mRNA increased in response to BDNF stimulation. The BDNF-induced increase in cell migration was antagonized by a HO-1 inhibitor and HO-1 siRNA. Furthermore, the expression of vascular endothelial growth factor (VEGF) also increased in response to BDNF stimulation, as did VEGF mRNA expression and transcriptional activity. The increase in BDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Moreover, transfection with HO-1 siRNA effectively reduced the increased VEGF expression induced by BDNF. The BDNF-induced cell migration was regulated by the ERK, p38, and Akt signaling pathways. Furthermore, BDNF-increased HO-1 and VEGF promoter transcriptional activity were inhibited by ERK, p38, and AKT pharmacological inhibitors and dominantnegative mutants in colon cancer cells. These results indicate that BDNF increases the migration of colon cancer cells by regulating VEGF/HO-1 activation through the ERK, p38, and PI3K/Akt signaling pathways. The results of this study may provide a relevant contribution to our understanding of the molecular mechanisms by which BDNF promotes colon cancer cell motility.

show abstract

“…TrkB immunoreactivity was correlated with advanced stage disease in lung squamous cell carcinomas, yet was also correlated with better survival (7). In contrast, TrkB expression was associated with worse survival in a panel of NSCLC samples containing squamous cell carcinomas, adenocarcinomas, and large-cell neuroendocrine carcinomas (8). Despite the evidence that TrkB is important for metastasis of cell lines, it has not been established that TrkB is required for NSCLC metastatic activity in endogenous tumors, and only xenograft models have been used to investigate TrkB function in other tumor types.…”

mentioning

confidence: 99%

Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis

Sinkevicius

Kriegel

Bellaria

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Lung cancer is notorious for its ability to metastasize, but the pathways regulating lung cancer metastasis are largely unknown. An in vitro system designed to discover factors critical for lung cancer cell migration identified brain-derived neurotrophic factor, which stimulates cell migration through activation of tropomyosinrelated kinase B (TrkB; also called NTRK2). Knockdown of TrkB in human lung cancer cell lines significantly decreased their migratory and metastatic ability in vitro and in vivo. In an autochthonous lung adenocarcinoma model driven by activated oncogenic Kras and p53 loss, TrkB deficiency significantly reduced metastasis. Hypoxiainducible factor-1 directly regulated TrkB expression, and, in turn, TrkB activated Akt signaling in metastatic lung cancer cells. Finally, TrkB expression was correlated with metastasis in patient samples, and TrkB was detected more often in tumors that did not have Kras or epidermal growth factor receptor mutations. These studies demonstrate that TrkB is an important therapeutic target in metastatic lung adenocarcinoma.TrkB/NTRK2 | NSCLC L ung cancer remains the major cause of death from cancer worldwide. The two types of lung cancer are non-small-cell lung cancers (NSCLCs; 80% of all lung cancers), which include adenocarcinomas, squamous cell carcinomas, and large cell carcinomas, and small-cell lung cancers (20%, exhibiting neuroendocrine features). The average 5-y survival rate for NSCLC is only 16% (1). Most NSCLC patients have advanced disease at diagnosis; 22% have regional lymph node metastases, and 56% have distant metastases in the brain, bone, liver, or adrenal glands (1). Surgery or therapies that treat primary lung tumors rarely prevent metastases (1). Understanding the mechanisms of NSCLC metastasis is crucial for the development of new therapies to improve survival for lung cancer patients.Tropomyosin-related kinase B (TrkB; also called NTRK2), a neurotrophin receptor, is important for neural development and is an independent prognostic marker in many tumor types (2). TrkB-expressing neural precursors migrate from their proliferative zone toward a gradient of the TrkB ligand, brainderived neurotrophic factor (BDNF), which is made near the site of residence of the mature neurons (3). High levels of TrkB are correlated with poor patient prognosis in neuroblastomas and ovarian, pancreatic, colon, prostate, and gastric cancers (2). TrkB was overexpressed in ovarian adenocarcinoma metastases compared with primary lesions (4). TrkB is also a supressor of anoikis in cell lines (5). Finally, overexpression of TrkB and BDNF in nonmalignant rat intestinal epithelial cells promoted metastasis from s.c. injection sites to the lungs (6).Despite these clues that TrkB regulates parts of the metastatic cascade in other tumor types, the role of TrkB in NSCLC metastasis remains unclear. TrkB immunoreactivity was correlated with advanced stage disease in lung squamous cell carcinomas, yet was also correlated with better survival (7). In contrast, TrkB expression was as...

show abstract

Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer

Cited by 89 publications

References 36 publications

BDNF: An Oncogene or Tumor Suppressor?

BDNF: An Oncogene or Tumor Suppressor?

Brain-derived neurotrophic factor regulates cell motility in human colon cancer

Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis

Contact Info

Product

Resources

About