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Updated: Feb 3, 2026

T-wave Ion Mobility-mass Spectrometry: Basic Experimental Procedures for Protein Complex Analysis
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Published on: July 31, 2010

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RalB directly triggers invasion downstream Ras by mobilizing the Wave complex

Giulia Zago1,2, Irina Veith1,2, Manish Kumar Singh1,2

  • 1Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Paris, France.

Elife
|October 16, 2018
PubMed

Insights

Researchers identified a novel pathway involving RalB that drives cancer invasion and metastasis. This discovery highlights the Ras-RGL1/2-RalB-exocyst-Wave Regulatory Complex axis as a potential target for new cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Ral GTPases (RalA and RalB) are critical downstream effectors of Ras oncoproteins in human cancers.
  • RalB specifically contributes to cancer invasion and metastasis, yet targeted therapies are lacking.

Purpose of the Study:

  • To elucidate the signaling pathways through which Ras promotes cancer invasion and metastasis.
  • To identify novel therapeutic targets for Ral-mediated cancer progression.

Main Methods:

  • Utilized a novel optogenetic approach for light-controlled activation of Ral at the plasma membrane.
  • Investigated the recruitment of the Wave Regulatory Complex (WRC) via the exocyst effector.
  • Analyzed RalB protein expression in human breast cancer tissues.

Main Results:

  • Light-induced Ral activation promotes WRC recruitment, leading to cellular protrusions and invasion.
  • Active Ras signals to RalB through RalGEFs (RGL1 and RGL2) to enhance invasiveness.
  • RalB's role in invasiveness is more significant than MAPK and PI3K pathways.
  • Increased RalB protein expression correlates with metastatic progression in breast cancer.

Conclusions:

  • The Ras-RGL1/2-RalB-exocyst-WRC signaling axis is a key driver of cancer invasion and metastasis.
  • RalB represents a promising therapeutic target for developing novel anticancer strategies.
Keywords:
ExocystInvasionRalWavebreast cancercell biologyhumanoptogenetics

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