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Published on: November 11, 2018
Ras and Rho GTPases on the move: The RasGRF connection
Piero Crespo1, Fernando Calvo, Victoria Sanz-Moreno
1Instituto de Biomedicina y Biotecnologıa de Cantabria (IBBTEC); Consejo Superior de Investigaciones Cientıficas (CSIC)-IDICAN-Universidad de Cantabria; Departamento de Biologıa Molecular; Facultad de Medicina; Santander, Cantabria Spain.
Abstract:
Metastasis involves tumor cells moving through tissues and crossing tissue boundaries, which requires cell migration, remodeling of cell-to-cell contacts and interactions with the extracellular matrix. Individual tumor cells move in three-dimensional environments with either a rounded "ameboid" or an elongated "mesenchymal" morphology. These two modes of movement are tightly regulated by Rho family GTPases: elongated movement requires activation of Rac1, whereas rounded movement engages specific Cdc42 and Rho signaling pathways. It has been known for some time that events unfolding downstream of Ras GTPases are also involved in regulating multiple aspects of cell migration and invasion. More recently, RasGRF2-a Ras activator-has been identified as a suppressor of rounded movement, by inhibiting the activation of Cdc42, independently of its capacity to activate Ras. Here, we discuss how Rho and Ras signals can either cooperate or oppose each other in the regulation of cell migration and invasion.
Insights
Tumor cell metastasis involves distinct migration modes, ameboid and mesenchymal, regulated by Rho and Ras signaling pathways. RasGRF2 specifically suppresses ameboid movement by inhibiting Cdc42, highlighting complex crosstalk in cancer invasion.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Signaling
Background:
- Metastasis requires tumor cell migration and extracellular matrix interaction.
- Tumor cells exhibit ameboid (rounded) or mesenchymal (elongated) movement.
- Rho family GTPases (Rac1, Cdc42, Rho) regulate these distinct migration modes.
Purpose of the Study:
- To explore the interplay between Rho and Ras signaling in regulating tumor cell migration.
- To elucidate the role of RasGRF2 in controlling cell morphology during invasion.
Main Methods:
- Analysis of Rho and Ras GTPase signaling pathways.
- Investigating the function of RasGRF2 in cell migration assays.
- Studying the impact of signaling crosstalk on cell morphology.
Main Results:
- RasGRF2 acts as a suppressor of ameboid (rounded) cell movement.
- RasGRF2 inhibits Cdc42 activation, independent of its Ras-activating function.
- Rho and Ras signals exhibit cooperative and opposing interactions in regulating cell invasion.
Conclusions:
- RasGRF2 plays a crucial role in suppressing rounded cell migration by modulating Cdc42 signaling.
- The intricate crosstalk between Ras and Rho pathways is critical for controlling tumor cell invasion and metastasis.
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