New insights into Nm23 control of cell adhesion and migration.
The molecular mechanisms underlying the role of Nm23/NDP kinase in controlling cell migration and metastasis have been investigated. The recent progress in our understanding of cell migration at a molecular level gives us some clues to the putative Nm23 function as a suppressor of metastasis. Screening of the literature indicates that NDP kinases have pleiotropic effects. By modifying cytoskeleton organization and protein trafficking, some NDP kinase isoforms may indirectly promote adhesion to the extracellular matrix in some cell types. Conversely, Nm23 regulates cell surface expression of integrin receptors and matrix metallo-proteases, and thus directly controls the cell adhesion machinery. Finally, the recent discovery of the interaction between Nm23-H2 and the negative regulator of beta1 integrin-mediated cell adhesion, ICAP-1, which targets the kinase to lamellipodia and cell protrusions, suggests that the Nm23-H2/ICAP-1 complex plays a role in integrin signaling, and exerts a fine-tuning between migration and spreading.
Fournier
Henri-Noël
HN
Laboratoire de la Différenciation et de l'Adherence Cellulaires, UMR CNRS/UJF 5538, Institut Albert Bonniot, Faculté de Médecine de Grenoble, F38706 La Tronche Cedex, France.
Albigès-Rizo
Corinne
C
Block
Marc R
MR
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008565:Membrane Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009369:Neoplasms / Q000378:metabolism; D009701:Nucleoside-Diphosphate Kinase; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D011506:Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C108257:ITGB1BP1 protein, human; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D011506:Proteins; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020782:Matrix Metalloproteinases