PMID- 25087096
OWN - NLM
STAT- MEDLINE
DCOM- 20150417
LR  - 20220408
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 35
IP  - 11
DP  - 2014 Nov
TI  - MEF2 transcription factors promotes EMT and invasiveness of hepatocellular 
      carcinoma through TGF-beta1 autoregulation circuitry.
PG  - 10943-51
LID - 10.1007/s13277-014-2403-1 [doi]
AB  - Invasion and metastasis is the main causes leading to the death of hepatocellular 
      carcinoma (HCC) patients. However, the underlying mechanism is still to be 
      explored. Transforming growth factor beta1 (TGF-beta1) is a stronger inducer of HCC 
      cell invasion. However, the downstream effector of TGF-beta1 that promotes HCC 
      invasion is still unknown. In this study, we found that PI3K/Akt activation takes 
      place following the stimulation of TGF-beta1. The inhibition of PI3K/Akt activation 
      abolished epithelial-mesenchymal transition (EMT) and invasion of HCC cells 
      induced by TGF-beta1. Myocyte enhancer factors 2 (MEF2) family proteins were found 
      to be overexpressed in HCC cells under the treatment of TGF-beta1 in a 
      PI3K/Akt-dependent way. Silencing the expression of MEF2s was able to prevent the 
      effect of TGF-beta1 on HCC EMT and invasion. Unexpectedly, MEF2 proteins were able 
      to promote the expression of TGF-beta1 in HCC cells, suggesting the existence of 
      regulatory circuitry consisting of TGF-beta1, PI3K/Akt, and MEF2. A natural 
      compound, oleanolic acid, was demonstrated to suppress the invasion and EMT of 
      HCC cells by downregulating MEF2, showing that targeting this pathway is an 
      effective therapeutic strategy for HCC invasion. We believe that our findings can 
      contribute to better understanding of the involved mechanism of HCC invasion and 
      the development of preventive and therapeutic strategy.
FAU - Yu, Wei
AU  - Yu W
AD  - Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of 
      Zhengzhou University, Henan Cancer Hospital, 127 Dongming Road, 450008, 
      Zhengzhou, China.
FAU - Huang, Changshan
AU  - Huang C
FAU - Wang, Qian
AU  - Wang Q
FAU - Huang, Tao
AU  - Huang T
FAU - Ding, Yuechao
AU  - Ding Y
FAU - Ma, Chao
AU  - Ma C
FAU - Ma, Hongbo
AU  - Ma H
FAU - Chen, Weiyu
AU  - Chen W
LA  - eng
PT  - Journal Article
DEP - 20140803
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 (MEF2 Transcription Factors)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Blotting, Western
MH  - Carcinoma, Hepatocellular/genetics/metabolism/*pathology
MH  - *Cell Movement
MH  - Cell Proliferation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - *Epithelial-Mesenchymal Transition
MH  - Flow Cytometry
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Liver Neoplasms/genetics/metabolism/*pathology
MH  - MEF2 Transcription Factors/genetics/*metabolism
MH  - Neoplasm Invasiveness
MH  - Oleanolic Acid/pharmacology
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/genetics/metabolism
MH  - RNA, Messenger/genetics
MH  - RNA, Small Interfering/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transforming Growth Factor beta1/genetics/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2014/08/05 06:00
MHDA- 2015/04/18 06:00
CRDT- 2014/08/04 06:00
PHST- 2014/05/17 00:00 [received]
PHST- 2014/07/24 00:00 [accepted]
PHST- 2014/08/04 06:00 [entrez]
PHST- 2014/08/05 06:00 [pubmed]
PHST- 2015/04/18 06:00 [medline]
AID - 10.1007/s13277-014-2403-1 [doi]
PST - ppublish
SO  - Tumour Biol. 2014 Nov;35(11):10943-51. doi: 10.1007/s13277-014-2403-1. Epub 2014 
      Aug 3.