Expression of the human gene encoding urokinase plasminogen activator receptor is activated by disruption of the cytoskeleton.
The transition of a stationary cell to a motile cell is associated with the breakdown of the cytoskeleton and expression of enzymes responsible for the degradation of the extracellular matrix. Reverse transcription PCR was used to address the question of whether disruption of the microfilament and microtubule systems is a signal for the increased expression of the urokinase plasminogen activator receptor (uPAR), a key molecule involved in extracellular matrix degradation. Disruption of the cytoskeleton of human fibroblasts with cytochalasin B (1 x 10(-5) M or 1 x 10(-7) M), colchicine (1 x 10(-5) M or 5 x 10(-7) M), or nocodazole (1 x 10(-6) M) resulted in major increases in the levels of uPAR mRNA with smaller increases in uPAR protein levels. Both cycloheximide and alpha-amanitin inhibited the increase in uPAR mRNA levels, demonstrating the requirement for the de novo synthesis of a short-lived protein for transcriptional activation. In contrast to normal fibroblasts, treatment of the metastatic cell line HT1080 with either cytochalasin B or colchicine produced little change in the high levels of uPAR mRNA expressed in these cells. These data suggest that cytoskeletal disruption may contribute to cell migration by signaling an increase in uPAR synthesis.
D000546:Amanitins / Q000494:pharmacology; D001483:Base Sequence; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D005347:Fibroblasts; D005354:Fibrosarcoma; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D000546:Amanitins; C524898:PLAUR protein, human; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D003571:Cytochalasin B; D003513:Cycloheximide; D015739:Nocodazole; D003078:Colchicine