PMID- 22533991
OWN - NLM
STAT- MEDLINE
DCOM- 20130117
LR  - 20220317
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 12
DP  - 2012 Apr 25
TI  - Carnitine palmitoyltransferase 1A (CPT1A): a transcriptional target of PAX3-FKHR 
      and mediates PAX3-FKHR-dependent motility in alveolar rhabdomyosarcoma cells.
PG  - 154
AB  - BACKGROUND: Alveolar rhabdomyosarcoma (ARMS) has a high propensity to 
      metastasize, leading to its aggressiveness and a poor survival rate among those 
      with the disease. More than 80% of aggressive ARMSs harbor a PAX3-FKHR fusion 
      transcription factor, which regulates cell migration and promotes metastasis, 
      most likely by regulating the fusion protein's transcriptional targets. 
      Therefore, identifying druggable transcription targets of PAX3-FKHR that are also 
      downstream effectors of PAX3-FKHR-mediated cell migration and metastasis may lead 
      to novel therapeutic approaches for treating ARMS. METHODS: To identify genes 
      whose expression is directly affected by the level of PAX3-FKHR in an ARMS 
      cellular-context, we first developed an ARMS cell line in which PAX3-FKHR is 
      stably down-regulated, and showed that stably downregulating PAX3-FKHR in ARMS 
      cells significantly decreased the cells' motility. We used microarray analysis to 
      identify genes whose expression level decreased when PAX3-FKHR was downregulated. 
      We used mutational analysis, promoter reporter assays, and electrophoretic 
      mobility shift assays to determine whether PAX3-FKHR binds to the promoter region 
      of the target gene. We used siRNA and pharmacologic inhibitor to downregulate the 
      target gene of PAX3-FKHR and investigated the effect of such downregulation on 
      cell motility. RESULTS: We found that when PAX3-FKHR was downregulated, the 
      expression of carnitine palmitoyltransferase 1A (CPT1A) decreased. We showed that 
      PAX3-FKHR binds to a paired-domain binding-site in the CPT1A promoter region, 
      indicating that CPT1A is a novel transcriptional target of PAX3-FKHR. 
      Furthermore, downregulating CPT1A decreased cell motility in ARMS cells, 
      indicating that CPT1A is a downstream effector of PAX3-FKHR-mediated cell 
      migration and metastasis. CONCLUSIONS: Taken together, we have identified CPT1A 
      as a novel transcriptional target of PAX3-FKHR and revealed the novel function of 
      CPT1A in promoting cell motility. CPT1A may represent a novel therapeutic target 
      for the treatment of ARMS.
FAU - Liu, Lingling
AU  - Liu L
AD  - Department of Chemical Biology and Therapeutics, St, Jude Children's Research 
      Hospital, Memphis, TN 38105, USA.
FAU - Wang, Yong-Dong
AU  - Wang YD
FAU - Wu, Jing
AU  - Wu J
FAU - Cui, Jimmy
AU  - Cui J
FAU - Chen, Taosheng
AU  - Chen T
LA  - eng
GR  - P30 CA021765/CA/NCI NIH HHS/United States
GR  - P30CA027165/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120425
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (PAX3-FKHR fusion protein, human)
RN  - 0 (Paired Box Transcription Factors)
RN  - EC 2.3.1.21 (CPT1A protein, human)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
SB  - IM
MH  - Binding Sites
MH  - Carnitine O-Palmitoyltransferase/*genetics
MH  - Cell Line, Tumor
MH  - Cell Movement/*genetics
MH  - Down-Regulation/genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Oncogene Proteins, Fusion/genetics/*metabolism
MH  - Paired Box Transcription Factors/metabolism
MH  - Response Elements
MH  - Rhabdomyosarcoma, Alveolar/*genetics/*metabolism
MH  - *Transcription, Genetic
MH  - Transcriptional Activation
PMC - PMC3453510
EDAT- 2012/04/27 06:00
MHDA- 2013/01/18 06:00
PMCR- 2012/04/25
CRDT- 2012/04/27 06:00
PHST- 2011/10/17 00:00 [received]
PHST- 2012/04/25 00:00 [accepted]
PHST- 2012/04/27 06:00 [entrez]
PHST- 2012/04/27 06:00 [pubmed]
PHST- 2013/01/18 06:00 [medline]
PHST- 2012/04/25 00:00 [pmc-release]
AID - 1471-2407-12-154 [pii]
AID - 10.1186/1471-2407-12-154 [doi]
PST - epublish
SO  - BMC Cancer. 2012 Apr 25;12:154. doi: 10.1186/1471-2407-12-154.