Adhesion of cells to an extracellular matrix is characterized by several discrete morphological and functional stages beginning with cell-substrate attachment, followed by cell spreading, migration, and immobilization. We find that although @entity1426 release is rate-limiting in the overall process of adhesion, its oxidation by lipoxygenase and cyclooxygenases regulates, respectively, the cell spreading and cell migration stages. During the adhesion of NIH-3T3 cells to fibronectin, two functionally and kinetically distinct phases of @entity1426 release take place. An initial transient @entity3899 release occurs during cell attachment to fibronectin, and is sufficient to signal the cell spreading stage after its oxidation by @entity25084 to leukotrienes. A later sustained @entity3899 release occurs during and after spreading, and signals the subsequent migration stage through its oxidation to @entity2918 by newly synthesized @entity1996 . In signaling migration, constitutively expressed @entity48901 appears to contribute approximately 25% of prostaglandins synthesized compared with the inducible @entity1996 . Both the second sustained @entity3899 release, and @entity1996 protein induction and synthesis, appear to be regulated by the mitogen-activated protein kinase @entity8837 . The initial cell attachment-induced transient @entity1426 release that signals spreading through lipoxygenase oxidation is not sensitive to @entity8837 inhibition by @entity4286 , whereas @entity4286 produces both a reduction in the larger second @entity3899 release and a blockade of induced @entity1996 protein expression with concomitant reduction of @entity3009 synthesis. The second @entity3899 release, and @entity1996 expression and activity, both appear to be required for cell migration but not for the preceding stages of attachment and spreading. These data suggest a bifurcation in the @entity1426 adhesion-signaling pathway, wherein lipoxygenase oxidation generates @entity4352 metabolites regulating the spreading stage of cell adhesion, whereas @entity8837 -induced cyclooxygenase synthesis results in oxidation of a later release, generating @entity3009 metabolites regulating the later migration stage.

Modulation of cell-substrate adhesion by XXXX : lipoxygenase regulates cell spreading and @entity8837 -inducible cyclooxygenase regulates cell migration in NIH-3T3 fibroblasts.

@entity25084 :: ('11689(Tax:10090)', 'Gene') :: ['5-lipoxygenase'] @entity48901 :: ('19224(Tax:10090)', 'Gene') :: ['cyclooxygenase-1'] @entity1426 :: ('MESH:D016718', 'Chemical') :: ['arachidonic acid'] @entity2918 :: ('MESH:D011453', 'Chemical') :: ['prostaglandins'] @entity3009 :: ('CHEBI:26333', 'Chemical') :: ['prostaglandin'] @entity4352 :: ('CHEBI:25029', 'Chemical') :: ['leukotriene'] @entity3899 :: ('CHEBI:32395', 'Chemical') :: ['arachidonate'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD98059'] @entity1996 :: ('19225(Tax:10090)', 'Gene') :: ['cyclooxygenase-2'] @entity8837 :: ('26417;26413', 'Gene') :: ['ERK1/2', 'extracellular signal-regulated kinase (ERK)1/2', 'ERK 1/2']
@entity1426 :: (MESH:D016718,Chemical) :: ['arachidonic acid']
