PMID- 28521610
OWN - NLM
STAT- MEDLINE
DCOM- 20180329
LR  - 20181202
IS  - 1554-8635 (Electronic)
IS  - 1554-8627 (Print)
IS  - 1554-8627 (Linking)
VI  - 13
IP  - 5
DP  - 2017 May 4
TI  - SPHK1 (sphingosine kinase 1) induces epithelial-mesenchymal transition by 
      promoting the autophagy-linked lysosomal degradation of CDH1/E-cadherin in 
      hepatoma cells.
PG  - 900-913
LID - 10.1080/15548627.2017.1291479 [doi]
AB  - SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a 
      causal role in the development of hepatocellular carcinoma (HCC) through 
      augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 
      signaling promotes invasion and metastasis in HCC remains to be clarified. Here, 
      we reported that SPHK1 induced the epithelial-mesenchymal transition (EMT) by 
      accelerating CDH1/E-cadherin lysosomal degradation and facilitating the invasion 
      and metastasis of HepG2 cells. Initially, we found that SPHK1 promoted cell 
      migration and invasion and induced the EMT process through decreasing the 
      expression of CDH1, which is an epithelial marker. Furthermore, SPHK1 accelerated 
      the lysosomal degradation of CDH1 to induce EMT, which depended on TRAF2 (TNF 
      receptor associated factor 2)-mediated macroautophagy/autophagy activation. In 
      addition, the inhibition of autophagy recovered CDH1 expression and reduced cell 
      migration and invasion through delaying the degradation of CDH1 in 
      SPHK1-overexpressing cells. Moreover, the overexpression of SPHK1 produced 
      intracellular sphingosine-1-phosphate (S1P). In response to S1P stimulation, 
      TRAF2 bound to BECN1/Beclin 1 and catalyzed the lysine 63-linked ubiquitination 
      of BECN1 for triggering autophagy. The deletion of the RING domain of TRAF2 
      inhibited autophagy and the interaction of BECN1 and TRAF2. Our findings define a 
      novel mechanism responsible for the regulation of the EMT via 
      SPHK1-TRAF2-BECN1-CDH1 signal cascades in HCC cells. Our work indicates that the 
      blockage of SPHK1 activity to attenuate autophagy may be a promising strategy for 
      the prevention and treatment of HCC.
FAU - Liu, Hong
AU  - Liu H
AD  - a Key Laboratory of Biotechnology of Antibiotics of National Health and Family 
      Planning Commission (NHFPC) , Department of Oncology , Institute of Medicinal 
      Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences 
      , Beijing , China.
FAU - Ma, Yan
AU  - Ma Y
AD  - a Key Laboratory of Biotechnology of Antibiotics of National Health and Family 
      Planning Commission (NHFPC) , Department of Oncology , Institute of Medicinal 
      Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences 
      , Beijing , China.
FAU - He, Hong-Wei
AU  - He HW
AD  - a Key Laboratory of Biotechnology of Antibiotics of National Health and Family 
      Planning Commission (NHFPC) , Department of Oncology , Institute of Medicinal 
      Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences 
      , Beijing , China.
FAU - Zhao, Wu-Li
AU  - Zhao WL
AD  - a Key Laboratory of Biotechnology of Antibiotics of National Health and Family 
      Planning Commission (NHFPC) , Department of Oncology , Institute of Medicinal 
      Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences 
      , Beijing , China.
FAU - Shao, Rong-Guang
AU  - Shao RG
AD  - a Key Laboratory of Biotechnology of Antibiotics of National Health and Family 
      Planning Commission (NHFPC) , Department of Oncology , Institute of Medicinal 
      Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences 
      , Beijing , China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - 0 (Antigens, CD)
RN  - 0 (CDH1 protein, human)
RN  - 0 (Cadherins)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (sphingosine kinase)
SB  - IM
MH  - Antigens, CD
MH  - Autophagy/*physiology
MH  - Cadherins/*metabolism
MH  - Carcinoma, Hepatocellular/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/physiology
MH  - *Epithelial-Mesenchymal Transition/physiology
MH  - Gene Expression Regulation, Neoplastic/physiology
MH  - Humans
MH  - Liver Neoplasms/metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
PMC - PMC5446059
OTO - NOTNLM
OT  - BECN1/Beclin 1
OT  - HepG2 cells
OT  - TRAF2
OT  - autophagy
OT  - invasion and metastasis
EDAT- 2017/05/20 06:00
MHDA- 2018/03/30 06:00
PMCR- 2017/02/28
CRDT- 2017/05/20 06:00
PHST- 2017/05/20 06:00 [entrez]
PHST- 2017/05/20 06:00 [pubmed]
PHST- 2018/03/30 06:00 [medline]
PHST- 2017/02/28 00:00 [pmc-release]
AID - 1291479 [pii]
AID - 10.1080/15548627.2017.1291479 [doi]
PST - ppublish
SO  - Autophagy. 2017 May 4;13(5):900-913. doi: 10.1080/15548627.2017.1291479.