PMID- 17461449
OWN - NLM
STAT- MEDLINE
DCOM- 20070605
LR  - 20220408
IS  - 1007-9327 (Print)
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Linking)
VI  - 13
IP  - 10
DP  - 2007 Mar 14
TI  - Roles of the MEK1/2 and AKT pathways in CXCL12/CXCR4 induced cholangiocarcinoma 
      cell invasion.
PG  - 1561-8
AB  - AIM: To evaluate the expression of C-X-C motif chemokine receptor 4 (CXCR4) and 
      its signaling cascades, which were previously identified as a key factor for 
      cancer cell progression and metastasis, in cholangiocarcinoma cell lines. 
      METHODS: The expression of CXCR4 and its signaling cascades were determined in 
      the cholangiocarcinoma cell lines (RMCCA1 and KKU100) by Western blotting. The 
      invasion assays and the detection of actin polymerization were tested in these 
      cholangiocarcinoma cells treated with CXC chemokine ligand -12 (CXCL12). RESULTS: 
      Expression of CXCR4 was detected in both cholangiocarcinoma cell lines and 
      activation of CXCR4 with CXCL12 triggered the signaling via the extracellular 
      signal-regulated kinase-1/2 (ERK1/2) and phosphoinositide 3-kinase (PI3K) and 
      induction of cholangiocarcinoma cell invasion, and displayed high levels of actin 
      polymerization. Addition of CXCR4 inhibitor (AMD3100) abrogated CXCL12-induced 
      phosphorylation of MEK1/2 and Akt in these cells. Moreover, treatment with MEK1/2 
      inhibitor (U0126) or PI3K inhibitor (LY294002) also attenuated the effect of 
      CXCL12-induced cholangiocarcinoma cell invasion. CONCLUSION: These results 
      indicated that the activation of CXCR4 and its signaling pathways (MEK1/2 and 
      Akt) are essential for CXCL12-induced cholangiocarcinoma cell invasion. This 
      rises Implications on a potential role for the inhibition of CXCR4 or its signal 
      cascades in the treatment of cholangiocarcinoma.
FAU - Leelawat, Kawin
AU  - Leelawat K
AD  - Department of Surgery, Rajavithi Hospital, Bangkok 10400, Thailand. 
      sckll@mahidol.ac.th
FAU - Leelawat, Surang
AU  - Leelawat S
FAU - Narong, Siriluck
AU  - Narong S
FAU - Hongeng, Suradej
AU  - Hongeng S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Benzylamines)
RN  - 0 (Butadienes)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Chromones)
RN  - 0 (Cyclams)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Heterocyclic Compounds)
RN  - 0 (Morpholines)
RN  - 0 (Nitriles)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (U 0126)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - S915P5499N (plerixafor)
SB  - IM
MH  - Benzylamines
MH  - Bile Duct Neoplasms/genetics/*pathology/physiopathology
MH  - Bile Ducts, Intrahepatic
MH  - Butadienes/pharmacology
MH  - Cell Line, Tumor
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/genetics/*physiology
MH  - Cholangiocarcinoma/genetics/*pathology/physiopathology
MH  - Chromones/pharmacology
MH  - Cyclams
MH  - Cytoskeleton/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation, Neoplastic/physiology
MH  - Heterocyclic Compounds/pharmacology
MH  - Humans
MH  - MAP Kinase Kinase 1/antagonists & inhibitors/genetics/*physiology
MH  - MAP Kinase Kinase 2/antagonists & inhibitors/genetics/*physiology
MH  - Morpholines/pharmacology
MH  - Neoplasm Invasiveness/genetics/physiopathology
MH  - Nitriles/pharmacology
MH  - Oncogene Protein v-akt/genetics/*physiology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Receptors, CXCR4/antagonists & inhibitors/genetics/*physiology
MH  - Signal Transduction/physiology
PMC - PMC4146899
EDAT- 2007/04/28 09:00
MHDA- 2007/06/06 09:00
PMCR- 2007/03/14
CRDT- 2007/04/28 09:00
PHST- 2007/04/28 09:00 [pubmed]
PHST- 2007/06/06 09:00 [medline]
PHST- 2007/04/28 09:00 [entrez]
PHST- 2007/03/14 00:00 [pmc-release]
AID - 10.3748/wjg.v13.i10.1561 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2007 Mar 14;13(10):1561-8. doi: 10.3748/wjg.v13.i10.1561.