PMID- 21217780
OWN - NLM
STAT- MEDLINE
DCOM- 20110623
LR  - 20211203
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 30
IP  - 17
DP  - 2011 Apr 28
TI  - c-Met-induced epithelial carcinogenesis is initiated by the serine protease 
      matriptase.
PG  - 2003-16
LID - 10.1038/onc.2010.586 [doi]
AB  - The progression and negative outcome of a variety of human carcinomas are 
      intimately associated with aberrant activity of the c-Met oncogene. The 
      underlying cause of this dysregulation, however, remains a subject of discussion, 
      as the majority of cancer patients do not present with activating mutations in 
      c-Met receptor itself. In this study, we show that the oncogenic protease 
      matriptase is ubiquitously co-expressed with the c-Met in human squamous cell 
      carcinomas and amplifies migratory and proliferative responses of primary 
      epithelial cells to the cognate ligand for c-Met, pro-hepatocyte growth 
      factor/scatter factor (proHGF/SF), through c-Met and Gab1 signaling. Furthermore, 
      the selective genetic ablation of c-Met from matriptase-expressing keratinocytes 
      completely negates the oncogenic potential of matriptase. In addition, 
      matriptase-dependent carcinoma formation could be blocked by the pharmacological 
      inhibition of the Akt-mammalian target of Rapamycin (mTor) pathway. Our data 
      identify matriptase as an initiator of c-Met-Akt-mTor-dependent signaling axis in 
      tumors and reveal mTor activation as an essential component of 
      matriptase/c-Met-induced carcinogenesis. The study provides a specific example of 
      how epithelial transformation can be promoted by epigenetic acquisition of the 
      capacity to convert a widely available paracrine growth factor precursor to its 
      signaling competent state.
FAU - Szabo, R
AU  - Szabo R
AD  - Oral and Pharyngeal Cancer Branch, NIDCR, NIH, Bethesda, MD 20892, USA.
FAU - Rasmussen, A L
AU  - Rasmussen AL
FAU - Moyer, A B
AU  - Moyer AB
FAU - Kosa, P
AU  - Kosa P
FAU - Schafer, J M
AU  - Schafer JM
FAU - Molinolo, A A
AU  - Molinolo AA
FAU - Gutkind, J S
AU  - Gutkind JS
FAU - Bugge, T H
AU  - Bugge TH
LA  - eng
GR  - ZIA DE000699-11/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20110110
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Protein Precursors)
RN  - 0 (pro-hepatocyte growth factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.- (matriptase)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/enzymology/genetics/*pathology
MH  - *Cell Transformation, Neoplastic
MH  - Epithelial Cells/*enzymology/*pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - Head and Neck Neoplasms/enzymology/genetics/*pathology
MH  - Hepatocyte Growth Factor/metabolism
MH  - Humans
MH  - Keratinocytes/enzymology/metabolism/pathology
MH  - Mice
MH  - Protein Precursors/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Proto-Oncogene Proteins c-met/deficiency/genetics/*metabolism
MH  - Serine Endopeptidases/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Up-Regulation
PMC - PMC3084339
MID - NIHMS254452
EDAT- 2011/01/11 06:00
MHDA- 2011/06/24 06:00
PMCR- 2011/10/28
CRDT- 2011/01/11 06:00
PHST- 2011/01/11 06:00 [entrez]
PHST- 2011/01/11 06:00 [pubmed]
PHST- 2011/06/24 06:00 [medline]
PHST- 2011/10/28 00:00 [pmc-release]
AID - onc2010586 [pii]
AID - 10.1038/onc.2010.586 [doi]
PST - ppublish
SO  - Oncogene. 2011 Apr 28;30(17):2003-16. doi: 10.1038/onc.2010.586. Epub 2011 Jan 
      10.