1. Activation of small GTPase Rho is required for autocrine motility factor signaling.
- Author
-
Tsutsumi S, Gupta SK, Hogan V, Collard JG, and Raz A
- Subjects
- ADP Ribose Transferases pharmacology, Cell Movement physiology, Cytoskeleton enzymology, Cytoskeleton pathology, Enzyme Activation, Fibrosarcoma enzymology, Fibrosarcoma metabolism, Fibrosarcoma pathology, Humans, Melanoma enzymology, Melanoma metabolism, Melanoma pathology, Receptors, Autocrine Motility Factor, Receptors, Cytokine physiology, Signal Transduction physiology, Stress Fibers enzymology, Stress Fibers metabolism, Stress Fibers pathology, Ubiquitin-Protein Ligases, cdc42 GTP-Binding Protein metabolism, rac1 GTP-Binding Protein biosynthesis, rac1 GTP-Binding Protein metabolism, rho GTP-Binding Proteins metabolism, rhoA GTP-Binding Protein metabolism, Botulinum Toxins, Glucose-6-Phosphate Isomerase physiology, rho GTP-Binding Proteins physiology
- Abstract
The hallmark of tumor metastasis is the dissemination of cells from the primary growth site to distant organs. Autocrine motility factor (AMF), a tumor-associated C-X-X-C cytokine, the ligand for a unique 78 kDa seven transmembrane receptor, is a potent simulator of cell motility, a process that is a prerequisite for tumor progression and metastasis. Because little is known about AMF-dependent signaling, we sought to study whether AMF signaling involves family members of the Rho-like GTPases. AMF stimulation of human melanoma cells resulted in stress-fiber formation, concomitant with up-regulation and activation of both RhoA and Rac1 expression with no apparent changes in the expression level or activation state of Cdc42. Treatment of the cells with C3 exoenzyme before AMF stimulation inhibited both the formation of stress-fiber-like structures and the activation of RhoA. In addition, both c-Jun NH(2)-terminal kinase 1 and c-Jun NH(2)-terminal kinase 2 were simultaneously activated by AMF, supporting the notion that they are involved in the signaling pathway of RhoA. We thus conclude that AMF signaling shares a similar pathway to previously established paracrine factors signaling involving cytoskeletal rearrangement and morphological alterations mediated by the small RhoA-like GTPases.
- Published
- 2002