PMID- 16691505
OWN - NLM
STAT- MEDLINE
DCOM- 20070404
LR  - 20231213
IS  - 0282-0080 (Print)
IS  - 0282-0080 (Linking)
VI  - 23
IP  - 3-4
DP  - 2006 May
TI  - Nuclear factor inducing kinase: a key regulator in osteopontin- induced 
      MAPK/IkappaB kinase dependent NF-kappaB-mediated promatrix metalloproteinase-9 
      activation.
PG  - 221-32
AB  - Osteopontin (OPN) is a secreted, non-collagenous, sialic-acid rich, glycosylated 
      adhesive phospho- protein. Several highly metastatic transformed cells 
      synthesized a higher level of OPN compared with non-tumorigenic cells. We have 
      recently reported that OPN induces nuclear factor-kappaB (NF-kappaB)-mediated 
      promatrix metalloproteinase-2 activation through IkappaBalpha/IKK signaling 
      pathways. However, the molecular mechanism(s) by which OPN regulates pro-matrix 
      metalloproteinase-9 (pro-MMP-9) activation and involvement of upstream kinases in 
      regulation of these processes that ultimately control cell motility and tumor 
      growth in murine melanoma cells are not well defined. Here we report that OPN 
      induces alphavbeta3 integrin-mediated phosphorylation and activation of nuclear 
      factor inducing kinase (NIK) and enhances the interaction between phosphorylated 
      NIK and IkappaBalpha kinase alpha/beta (IKKalpha/beta) in B16F10 cells. Moreover, 
      NIK is involved in OPN-induced phosphorylations of MEK-1 and ERK1/2 in these 
      cells. OPN induces NIK-dependent NF-kappaB activation through 
      ERK/IKKalpha/beta-mediated pathways. Furthermore, OPN enhances NIK-regulated 
      urokinase-type plasminogen activator (uPA) secretion, uPA-dependent pro-MMP-9 
      activation, and cell motility. Pretreatment of cells with anti-MMP-2 antibody 
      along with anti-MMP-9 antibody drastically inhibited the OPN-induced cell 
      migration and chemoinvasion, whereas cells pretreated with anti-MMP-2 antibody 
      had no effect on OPN-induced pro-MMP-9 activation suggesting that OPN induces 
      pro-MMP-2 and pro-MMP-9 activations through two distinct pathways. Taken 
      together, NIK acts as crucial regulator in OPN-induced MAPK/IKK-mediated 
      NF-kappaB-dependent uPA secretion and MMP-9 activation thereby controlling 
      melanoma cell motility and chemoinvasion.
FAU - Rangaswami, Hema
AU  - Rangaswami H
AD  - National Center for Cell Science (NCCS), Pune, 411 007, India.
FAU - Bulbule, Anuradha
AU  - Bulbule A
FAU - Kundu, Gopal C
AU  - Kundu GC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Glycoconj J
JT  - Glycoconjugate journal
JID - 8603310
RN  - 0 (Enzyme Precursors)
RN  - 0 (Integrins)
RN  - 0 (NF-kappa B)
RN  - 106441-73-0 (Osteopontin)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - EC 3.4.24.- (pro-matrix metalloproteinase 9)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
EIN - Glycoconj J. 2007 Nov;24(8):509
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - DNA/metabolism
MH  - Enzyme Activation/drug effects
MH  - Enzyme Precursors/*metabolism
MH  - I-kappa B Kinase/*metabolism
MH  - Integrins/metabolism
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Melanoma/metabolism/pathology
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/*metabolism
MH  - Osteopontin/*metabolism/pharmacology
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Urokinase-Type Plasminogen Activator/metabolism
MH  - NF-kappaB-Inducing Kinase
EDAT- 2006/05/13 09:00
MHDA- 2007/04/05 09:00
CRDT- 2006/05/13 09:00
PHST- 2006/05/13 09:00 [pubmed]
PHST- 2007/04/05 09:00 [medline]
PHST- 2006/05/13 09:00 [entrez]
AID - 10.1007/s10719-006-7927-1 [doi]
PST - ppublish
SO  - Glycoconj J. 2006 May;23(3-4):221-32. doi: 10.1007/s10719-006-7927-1.