PMID- 19946339
OWN - NLM
STAT- MEDLINE
DCOM- 20100423
LR  - 20240223
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 29
IP  - 9
DP  - 2010 Mar 4
TI  - Overexpression of macrophage inhibitory cytokine-1 induces metastasis of human 
      prostate cancer cells through the FAK-RhoA signaling pathway.
PG  - 1293-302
LID - 10.1038/onc.2009.420 [doi]
AB  - An elevated level of macrophage inhibitory cytokine-1 (MIC-1) is reported in the 
      sera of patients with metastatic prostate cancer compared with that of benign 
      diseases and healthy adults. We investigated the mechanistic role of MIC-1 
      overexpression in the metastasis of prostate cancer cells. Our study showed a 
      progressive increase in secretory MIC-1 production correlated with the increase 
      in the metastatic potential of PC-3 and LNPCa prostate cancer metastatic 
      variants. Further, the in vitro studies using 'loss-' and 'gain'-of-function 
      approaches showed that ectopic overexpression of MIC-1 (PC-3-MIC-1) and forced 
      downregulation of MIC-1(PC-3M-siMIC-1) enhanced and reduced the motility and 
      invasiveness of these cells, respectively. Supporting our in vitro observations, 
      all the mice orthotopically implanted with PC-3-MIC-1 cells developed metastasis 
      compared with none in the PC-3-vector group. Our results showed that MIC-1 
      overexpression was associated with apparent changes in actin organization. In 
      addition, an enhanced phosphorylation of focal adhesion kinase (FAK) and 
      guanosine-5'-triphosphate (GTP)-bound RhoA was also seen; however, no significant 
      change was observed in total FAK and RhoA levels in the PC-3-MIC-1 cells. 
      Altogether, our findings show that MIC-1 has a role in prostate cancer 
      metastasis, in part, by promoting the motility of these cells. Activation of the 
      FAK-RhoA signaling pathway is involved in MIC-1-mediated actin reorganization, 
      and thus, leads to an increase in the motility of prostate cancer cells.
FAU - Senapati, S
AU  - Senapati S
AD  - Department of Biochemistry and Molecular Biology, University of Nebraska Medical 
      Center, Omaha, NE 68198-5870, USA.
FAU - Rachagani, S
AU  - Rachagani S
FAU - Chaudhary, K
AU  - Chaudhary K
FAU - Johansson, S L
AU  - Johansson SL
FAU - Singh, R K
AU  - Singh RK
FAU - Batra, S K
AU  - Batra SK
LA  - eng
GR  - P30 CA036727/CA/NCI NIH HHS/United States
GR  - R01 CA078590/CA/NCI NIH HHS/United States
GR  - R01 CA078590-11S1/CA/NCI NIH HHS/United States
GR  - P30 CA36727/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20091130
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Growth Differentiation Factor 15)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects/physiology
MH  - Focal Adhesion Protein-Tyrosine Kinases/physiology
MH  - Gene Expression Regulation, Neoplastic
MH  - Growth Differentiation Factor 15/genetics/metabolism/*pharmacology/physiology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Neoplasm Invasiveness/pathology
MH  - Neoplasm Metastasis/*pathology/physiopathology
MH  - Phosphorylation
MH  - Prostatic Neoplasms/genetics/metabolism/*pathology
MH  - Signal Transduction/*drug effects/genetics
MH  - rhoA GTP-Binding Protein/physiology
PMC - PMC2896817
MID - NIHMS191876
COIS- Conflict of interest The authors declare no conflict of interest.
EDAT- 2009/12/01 06:00
MHDA- 2010/04/24 06:00
PMCR- 2010/07/05
CRDT- 2009/12/01 06:00
PHST- 2009/12/01 06:00 [entrez]
PHST- 2009/12/01 06:00 [pubmed]
PHST- 2010/04/24 06:00 [medline]
PHST- 2010/07/05 00:00 [pmc-release]
AID - onc2009420 [pii]
AID - 10.1038/onc.2009.420 [doi]
PST - ppublish
SO  - Oncogene. 2010 Mar 4;29(9):1293-302. doi: 10.1038/onc.2009.420. Epub 2009 Nov 30.