PMID- 15781656
OWN - NLM
STAT- MEDLINE
DCOM- 20050425
LR  - 20211203
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 65
IP  - 6
DP  - 2005 Mar 15
TI  - Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of 
      osteosarcoma.
PG  - 2406-11
AB  - Osteosarcoma is the most frequent primary malignant tumor of bone with a high 
      propensity for metastasis. We have previously showed that ezrin expression is 
      necessary for metastatic behavior in a murine model of osteosarcoma (K7M2). In 
      this study, we found that a mechanism of ezrin-related metastatic behavior is 
      linked to an Akt-dependent mammalian target of rapamycin (mTOR)/p70 ribosomal 
      protein S6 kinase (S6K1)/eukaryotic initiation factor 4E-binding protein 1 
      (4E-BP1) pathway. Suppression of ezrin expression either by antisense 
      transfection or by small interfering RNAs or disruption of ezrin function by 
      transfection of a dominant-negative ezrin-T567A mutant led to decreased 
      expression and decreased phosphorylation of both S6K1 and 4E-BP1. Proteosomal 
      inhibition by MG132 reversed antisense-mediated decrease of S6K1 and 4E-BP1 
      protein expression, but failed to affect the effect of ezrin on phosphorylation 
      of S6K1 and 4E-BP1. Blockade of the mTOR pathway with rapamycin or its analog, 
      cell cycle inhibitor-779 led to significant inhibition of experimental lung 
      metastasis in vivo. These results suggest that blocking the mTOR/S6K1/4E-BP1 
      pathway may be an appropriate target for strategies to reduce tumor cell 
      metastasis.
FAU - Wan, Xiaolin
AU  - Wan X
AD  - Molecular Oncology Section, Pediatric Oncology Branch, Center for Cancer 
      Research, National Cancer Institute, NIH, Bethesda, MD 20892-1106, USA.
FAU - Mendoza, Arnulfo
AU  - Mendoza A
FAU - Khanna, Chand
AU  - Khanna C
FAU - Helman, Lee J
AU  - Helman LJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Eif4ebp1 protein, mouse)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Antisense)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (ezrin)
RN  - 624KN6GM2T (temsirolimus)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Bone Neoplasms/genetics/*pathology
MH  - Carrier Proteins/antagonists & inhibitors/metabolism
MH  - Cell Cycle Proteins
MH  - Cytoskeletal Proteins
MH  - Eukaryotic Initiation Factors
MH  - Female
MH  - Mice
MH  - Mice, SCID
MH  - Osteosarcoma/genetics/*pathology
MH  - Phosphoproteins/*antagonists & inhibitors/genetics/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins/antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - RNA, Antisense/genetics
MH  - RNA, Small Interfering/genetics
MH  - Ribosomal Protein S6 Kinases, 70-kDa/antagonists & inhibitors/metabolism
MH  - Sirolimus/*analogs & derivatives/*pharmacology
MH  - Transfection
EDAT- 2005/03/23 09:00
MHDA- 2005/04/26 09:00
CRDT- 2005/03/23 09:00
PHST- 2005/03/23 09:00 [pubmed]
PHST- 2005/04/26 09:00 [medline]
PHST- 2005/03/23 09:00 [entrez]
AID - 65/6/2406 [pii]
AID - 10.1158/0008-5472.CAN-04-3135 [doi]
PST - ppublish
SO  - Cancer Res. 2005 Mar 15;65(6):2406-11. doi: 10.1158/0008-5472.CAN-04-3135.