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.

Bioarchitecture
|November 10, 2011
PubMed

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.

Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab Cascades01:25

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
GTPases and their Regulation02:14

GTPases and their Regulation

Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...