PMID- 10438456
OWN - NLM
STAT- MEDLINE
DCOM- 19990901
LR  - 20220224
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 33
DP  - 1999 Aug 13
TI  - Evidence that Smad2 is a tumor suppressor implicated in the control of cellular 
      invasion.
PG  - 22919-22
AB  - The Smad2 protein plays an essential role in the transforming growth factor-beta 
      (TGF-beta) signaling pathway. This pathway mediates growth inhibitory signals 
      from the cell surface to the nucleus. Although Smad2 protein is significantly 
      mutated in human cancers, there is no definitive evidence implicating Smad2 as a 
      tumor-suppressor gene. Here we show that overexpression of the tumor-derived 
      missense mutation Smad2.D450E, an unphosphorylable form of Smad2 found in 
      colorectal and lung cancers, did not abolish the TGF-beta-mediated growth arrest, 
      suggesting that resistance to the growth-inhibiting effects of TGF-beta exhibited 
      by human tumors cannot be linked to the inactivation of Smad2 protein. In 
      contrast, overexpression of Smad2.D450E induces cellular invasion, and this 
      effect was enhanced by TGF-beta. A similar invasive phenotype was obtained in 
      cells expressing another inactivating mutation in Smad2 (Smad2.P445H) found in 
      colorectal cancer. These findings indicate that genetic defects in Smad2 are 
      sufficient to confer the invasion-promoting effect of TGF-beta and reveal that 
      TGF-beta acts through Smad2 to induce cellular invasion by a novel mechanism that 
      is independent of Smad2 phosphorylation by the activated TGF-beta type I 
      receptor.
FAU - Prunier, C
AU  - Prunier C
AD  - INSERM U 482, Hopital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75571, 
      Paris Cedex 12, France.
FAU - Mazars, A
AU  - Mazars A
FAU - Noe, V
AU  - Noe V
FAU - Bruyneel, E
AU  - Bruyneel E
FAU - Mareel, M
AU  - Mareel M
FAU - Gespach, C
AU  - Gespach C
FAU - Atfi, A
AU  - Atfi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics/*physiology
MH  - Dogs
MH  - *Genes, Tumor Suppressor
MH  - Humans
MH  - Neoplasm Invasiveness/*genetics
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Smad2 Protein
MH  - Trans-Activators/genetics/*physiology
MH  - Transforming Growth Factor beta/physiology
EDAT- 1999/08/07 00:00
MHDA- 1999/08/07 00:01
CRDT- 1999/08/07 00:00
PHST- 1999/08/07 00:00 [pubmed]
PHST- 1999/08/07 00:01 [medline]
PHST- 1999/08/07 00:00 [entrez]
AID - S0021-9258(19)65236-1 [pii]
AID - 10.1074/jbc.274.33.22919 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 13;274(33):22919-22. doi: 10.1074/jbc.274.33.22919.