PMID- 22583359
OWN - NLM
STAT- MEDLINE
DCOM- 20120911
LR  - 20120515
IS  - 1600-0463 (Electronic)
IS  - 0903-4641 (Linking)
VI  - 120
IP  - 6
DP  - 2012 Jun
TI  - Knockdown of BDNF suppressed invasion of HepG2 and HCCLM3 cells, a mechanism 
      associated with inactivation of RhoA or Rac1 and actin skeleton disorganization.
PG  - 469-76
LID - 10.1111/j.1600-0463.2011.02855.x [doi]
AB  - Brain-derived neurotrophic factor (BDNF) and its primary receptor 
      tropomysin-related kinase B (TrkB) mediate critical signalings for supporting 
      survival and growth of neurons. Even though we have previously confirmed that 
      more expressions of BDNF and TrkB were closely correlated with multiple and 
      advanced hepatocellular carcinoma (HCC), the exact mechanisms underlying have not 
      been investigated. The expressions of BDNF and TrkB were examined by western blot 
      and BDNF secretion was evaluated by ELISA in human HCC cell lines of HepG2 and 
      HCCLM3 with high metastatic potential. BDNF knockdown was performed by specific 
      BDNF-siRNA transfection in HCC cells, actin cytoskeleton was shown by 
      FITC-phalloidin staining and the activations of RhoA, Rac1 or Cdc42 were 
      determined using western blot. Cell apoptosis and invasion were examined by flow 
      cytometry and transwell assay, respectively. More expressions of BDNF and TrkB 
      were found in HCCLM3 than in HepG2 cells. Inhibited expression of BDNF by 
      specific siRNA showed impaired actin polymerization and decreased activations of 
      RhoA or Rac1 in both HepG2 and HCCLM3 cells. BDNF knockdown also induced 
      apoptosis and suppressed invasion of both HepG2 and HCCLM3 cells. Our results 
      suggested a role of BDNF/TrkB in confering HCCLM3 cells advantage of metastasis, 
      and BDNF knockdown inhibited cell invasion probably through the blocked actin 
      polymerization and the correlated inactivation of RhoA or Rac1. Aiming at 
      BDNF/TrkB signaling interruption may be an effective strategy to prevent HCC 
      progression.
CI  - (c) 2011 The Authors. APMIS (c) 2011 APMIS.
FAU - Guo, Dawei
AU  - Guo D
AD  - Department of General Surgery, The Fourth Affiliated Hospital of China Medical 
      University, Shenyang, China.
FAU - Sun, Wenyu
AU  - Sun W
FAU - Zhu, Lei
AU  - Zhu L
FAU - Zhang, Hongbin
AU  - Zhang H
FAU - Hou, Xuezhong
AU  - Hou X
FAU - Liang, Jian
AU  - Liang J
FAU - Jiang, Xiaofeng
AU  - Jiang X
FAU - Liu, Chen
AU  - Liu C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111219
PL  - Denmark
TA  - APMIS
JT  - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
JID - 8803400
RN  - 0 (Actins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RAC1 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 124671-05-2 (RHOA protein, human)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Actins/genetics/*metabolism
MH  - Apoptosis/genetics
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/*deficiency/genetics/metabolism
MH  - Carcinoma, Hepatocellular/genetics/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Gene Knockdown Techniques
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/genetics/*metabolism/pathology
MH  - Neoplasm Invasiveness
MH  - RNA, Small Interfering/genetics
MH  - Receptor, trkB/biosynthesis/genetics/metabolism
MH  - Signal Transduction
MH  - cdc42 GTP-Binding Protein/genetics/metabolism
MH  - rac1 GTP-Binding Protein/genetics/*metabolism
MH  - rhoA GTP-Binding Protein/genetics/*metabolism
EDAT- 2012/05/16 06:00
MHDA- 2012/09/12 06:00
CRDT- 2012/05/16 06:00
PHST- 2012/05/16 06:00 [entrez]
PHST- 2012/05/16 06:00 [pubmed]
PHST- 2012/09/12 06:00 [medline]
AID - 10.1111/j.1600-0463.2011.02855.x [doi]
PST - ppublish
SO  - APMIS. 2012 Jun;120(6):469-76. doi: 10.1111/j.1600-0463.2011.02855.x. Epub 2011 
      Dec 19.