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Oncogenic K-Ras requires activation for enhanced activity

Oncogene volume 33, pages 532–535 (2014)Cite this article

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Abstract

Oncogenic Ras mutations are widely considered to be locked in a permanent ‘On’ state and ‘constitutively active’. Yet, many healthy people have cells possessing mutant Ras without apparent harm, and in animal models mutant Ras causes transformation only after upregulation of Ras activity. Here, we demonstrate that oncogenic K-Ras is not constitutively active but can be readily activated by upstream stimulants to lead to prolonged strong Ras activity. These data indicate that in addition to targeting K-Ras downstream effectors, interventions to reduce K-Ras activation may have important cancer-preventive value, especially in patients with oncogenic Ras mutations. As other small G proteins are regulated in a similar manner, this concept is likely to apply broadly to the entire Ras family of molecules.

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Acknowledgements

We thank Dr David Tuveson (UK Cambridge Research Institute) for providing the mouse pancreatic cancer cell line K8484. This work was supported by NIH DK052067, CA016672, P20 CA101936, CA155165, P50 CA102701 and the Lockton Endowment. The work was supported in part by grant 30910103911 (to Z Li) from the National Natural Science Foundation of China.

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Author notes

  1. B Ji and C D Logsdon: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    H Huang, J Daniluk, Y Liu, J Chu & C D Logsdon

  2. Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China

    H Huang & Z Li

  3. Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland

    J Daniluk

  4. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA

    B Ji

  5. Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    C D Logsdon

Authors
  1. H Huang
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  2. J Daniluk
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  3. Y Liu
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  4. J Chu
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  5. Z Li
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  6. B Ji
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  7. C D Logsdon
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Corresponding authors

Correspondence to B Ji or C D Logsdon.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Oncogene website

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Huang, H., Daniluk, J., Liu, Y. et al. Oncogenic K-Ras requires activation for enhanced activity. Oncogene 33, 532–535 (2014). https://doi.org/10.1038/onc.2012.619

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