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Updated: Jun 3, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
Rap1-GTP-interacting adaptor molecule (RIAM) protein controls invasion and growth of melanoma cells
Pablo Hernández-Varas1, Georgina P Coló, Ruben A Bartolomé
1Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, 28040 Madrid, Spain.
Abstract:
The Mig-10/RIAM/lamellipodin (MRL) family member Rap1-GTP-interacting adaptor molecule (RIAM) interacts with active Rap1, a small GTPase that is frequently activated in tumors such as melanoma and prostate cancer. We show here that RIAM is expressed in metastatic human melanoma cells and that both RIAM and Rap1 are required for BLM melanoma cell invasion. RIAM silencing in melanoma cells led to inhibition of tumor growth and to delayed metastasis in a severe combined immunodeficiency xenograft model. Defective invasion of RIAM-silenced melanoma cells arose from impairment in persistent cell migration directionality, which was associated with deficient activation of a Vav2-RhoA-ROCK-myosin light chain pathway. Expression of constitutively active Vav2 and RhoA in cells depleted for RIAM partially rescued their invasion, indicating that Vav2 and RhoA mediate RIAM function. These results suggest that inhibition of cell invasion in RIAM-silenced melanoma cells is likely based on altered cell contractility and cell polarization. Furthermore, we show that RIAM depletion reduces β1 integrin-dependent melanoma cell adhesion, which correlates with decreased activation of both Erk1/2 MAPK and phosphatidylinositol 3-kinase, two central molecules controlling cell growth and cell survival. In addition to causing inhibition of cell proliferation, RIAM silencing led to higher susceptibility to cell apoptosis. Together, these data suggest that defective activation of these kinases in RIAM-silenced cells could account for inhibition of melanoma cell growth and that RIAM might contribute to the dissemination of melanoma cells.
Insights
Rap1-GTP-interacting adaptor molecule (RIAM) is crucial for melanoma cell invasion and metastasis. Inhibiting RIAM in melanoma cells reduces tumor growth, migration, and increases apoptosis, suggesting RIAM as a therapeutic target.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- RIAM (Rap1-GTP-interacting adaptor molecule) is part of the Mig-10/RIAM/lamellipodin family.
- RIAM interacts with active Rap1, a GTPase implicated in melanoma and prostate cancer.
- RIAM is expressed in metastatic melanoma cells.
Purpose of the Study:
- To investigate the role of RIAM in melanoma cell invasion, metastasis, and tumor growth.
- To elucidate the molecular mechanisms underlying RIAM's function in melanoma.
Main Methods:
- RIAM silencing in melanoma cells.
- Severe combined immunodeficiency (SCID) xenograft models.
- Analysis of cell migration, invasion, adhesion, proliferation, and apoptosis.
- Western blotting to assess protein activation (Vav2, RhoA, Erk1/2, PI3K).
Main Results:
- RIAM and Rap1 are essential for melanoma cell invasion.
- RIAM silencing inhibited tumor growth and delayed metastasis in vivo.
- RIAM depletion impaired cell migration directionality via the Vav2-RhoA-ROCK pathway.
- RIAM silencing reduced β1 integrin-dependent adhesion, Erk1/2 MAPK, and PI3K activation.
- RIAM-silenced cells showed reduced proliferation and increased apoptosis.
Conclusions:
- RIAM plays a critical role in melanoma cell invasion, migration, and polarization.
- RIAM influences melanoma cell adhesion, growth, and survival through integrin and kinase signaling pathways.
- Targeting RIAM may offer a therapeutic strategy to inhibit melanoma progression and dissemination.
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