PMID- 29861866
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240326
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 38
DP  - 2018 May 18
TI  - TRKB tyrosine kinase receptor is a potential therapeutic target for poorly 
      differentiated oral squamous cell carcinoma.
PG  - 25225-25243
LID - 10.18632/oncotarget.25396 [doi]
AB  - It has been reported that one of the neurotrophin receptors, tropomyosin receptor 
      kinase B (TRKB), is frequently overexpressed in various tumor tissues including 
      oral squamous cell carcinoma (OSCC), and that its upregulation promotes tumor 
      progression in human cancers. However, the correlation between TRKB 
      overexpression and clinicopathological characteristics is not fully elucidated. 
      Here, we present the correlation between the expression levels of TRKB and/or its 
      secreted ligand, brain-derived neurotrophic factor (BDNF), and 
      clinicopathological characteristics, especially regarding tumor differentiation, 
      tissue invasion, and disease-free survival in patients with OSCC. The results 
      obtained through immunohistochemical analysis of human OSCC tumor specimens 
      showed that the expression levels of TRKB and/or BDNF, were significantly higher 
      in moderately and poorly differentiated OSCC (MD/PD-OSCC) tumor cells than in 
      well differentiated cells (WD-OSCC). Moreover, the OSCC tumors highly expressing 
      TRKB and/or BDNF exhibited promotion in tissue invasion and reduction in 
      disease-free survival in the patients. In an orthotopic transplantation mouse 
      model of human OSCC cell lines, administration of a TRKB-specific inhibitor 
      significantly suppressed the tumor growth and invasion in PD-OSCC-derived tumor 
      cells, but not in WD-OSCC-derived tumor cells. Moreover, the TRKB inhibitor 
      selectively blocked BDNF-induced tumor cell proliferation and migration 
      accompanied with the suppression of TRKB phosphorylation in PD-OSCC but not in 
      WD-OSCC in vitro. Taken together, these data suggest that the BDNF/TRKB signaling 
      pathway may regulate tumor progression in poorly differentiated OSCC. Expression 
      levels of signal molecules may be an accurate prognosis marker for tumor 
      aggressiveness, and the molecules may be an attractive target for new OSCC 
      therapies.
FAU - Moriwaki, Kazumasa
AU  - Moriwaki K
AD  - Department of Pharmacology, Faculty of Medicine, Osaka Medical College, 
      Takatsuki, Osaka 569-8686, Japan.
FAU - Ayani, Yusuke
AU  - Ayani Y
AD  - Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Osaka 
      Medical College, Osaka 569-8686, Japan.
FAU - Kuwabara, Hiroko
AU  - Kuwabara H
AD  - Department of Pathology, Faculty of Medicine, Osaka Medical College, Osaka 
      569-8686, Japan.
FAU - Terada, Tetsuya
AU  - Terada T
AD  - Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Osaka 
      Medical College, Osaka 569-8686, Japan.
FAU - Kawata, Ryo
AU  - Kawata R
AD  - Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Osaka 
      Medical College, Osaka 569-8686, Japan.
FAU - Asahi, Michio
AU  - Asahi M
AD  - Department of Pharmacology, Faculty of Medicine, Osaka Medical College, 
      Takatsuki, Osaka 569-8686, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180518
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5982746
OTO - NOTNLM
OT  - TRKB
OT  - anti-cancer drug
OT  - oral squamous cell carcinoma
OT  - prognostic factors
OT  - tumor differentiation
COIS- CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.
EDAT- 2018/06/05 06:00
MHDA- 2018/06/05 06:01
PMCR- 2018/05/18
CRDT- 2018/06/05 06:00
PHST- 2017/08/09 00:00 [received]
PHST- 2018/04/26 00:00 [accepted]
PHST- 2018/06/05 06:00 [entrez]
PHST- 2018/06/05 06:00 [pubmed]
PHST- 2018/06/05 06:01 [medline]
PHST- 2018/05/18 00:00 [pmc-release]
AID - 25396 [pii]
AID - 10.18632/oncotarget.25396 [doi]
PST - epublish
SO  - Oncotarget. 2018 May 18;9(38):25225-25243. doi: 10.18632/oncotarget.25396. 
      eCollection 2018 May 18.