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Sos-mediated cross-activation of wild-type Ras by oncogenic Ras is essential for tumorigenesis

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  • Hao-Hsuan Jeng

    (New York University School of Medicine
    Cell and Molecular Biology Training Program, New York University School of Medicine)

  • Laura J Taylor

    (New York University School of Medicine)

  • Dafna Bar-Sagi

    (New York University School of Medicine)

Abstract

Mammalian cells contain three closely related ras genes, H-ras, K-ras and N-ras. Although in a given tumour type, oncogenic mutations are selectively observed in only one of the ras genes, the acquisition of the transformed phenotype has been shown to require the contribution of the normal products of the other ras genes. Here we demonstrate that oncogenic K-Ras promotes the activation of wild-type H- and N-Ras. This activation is mediated by oncogenic K-Ras-dependent allosteric stimulation of Sos and confers a growth advantage to oncogenic K-Ras harbouring cancer cells. These findings underscore the complementary functions of oncogenic and wild-type Ras in tumour cells and identify a potential new targeting strategy for Ras-driven tumours.

Suggested Citation

  • Hao-Hsuan Jeng & Laura J Taylor & Dafna Bar-Sagi, 2012. "Sos-mediated cross-activation of wild-type Ras by oncogenic Ras is essential for tumorigenesis," Nature Communications, Nature, vol. 3(1), pages 1-8, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2173
    DOI: 10.1038/ncomms2173
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    Cited by:

    1. Brandon M. Murphy & Elizabeth M. Terrell & Venkat R. Chirasani & Tirzah J. Weiss & Rachel E. Lew & Andrea M. Holderbaum & Aastha Dhakal & Valentina Posada & Marie Fort & Michael S. Bodnar & Leiah M. C, 2022. "Enhanced BRAF engagement by NRAS mutants capable of promoting melanoma initiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Fernando C. Baltanás & Rósula García-Navas & Pablo Rodríguez-Ramos & Nuria Calzada & Cristina Cuesta & Javier Borrajo & Rocío Fuentes-Mateos & Andrea Olarte-San Juan & Nerea Vidaña & Esther Castellano, 2023. "Critical requirement of SOS1 for tumor development and microenvironment modulation in KRASG12D-driven lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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