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The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis

Oncogene volume 32, pages 903–909 (2013)Cite this article

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Abstract

Rac1b, an alternative splice form of Rac1, has been previously shown to be upregulated in colon and breast cancer cells, suggesting an oncogenic role for Rac1b in these cancers. Our analysis of NSCLC tumor and matched normal tissue samples indicates Rac1b is upregulated in a significant fraction of lung tumors in correlation with mutational status of K-ras. To directly assess the oncogenic potential of Rac1b in vivo, we employed a mouse model of lung adenocarcinoma, in which the expression of Rac1b can be conditionally activated specifically in the lung. Although expression of Rac1b alone is insufficient to drive tumor initiation, the expression of Rac1b synergizes with an oncogenic allele of K-ras resulting in increased cellular proliferation and accelerated tumor growth. Finally, we show that in contrast to our previous findings demonstrating a requirement for Rac1 in K-ras-driven cell proliferation, Rac1b is not required in this context. Given the partially overlapping spectrum of downstream effectors regulated by Rac1 and Rac1b, our findings further delineate the signaling pathways downstream of Rac1 that are required for K-ras driven tumorigenesis.

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Acknowledgements

We thank Dr Derek Radisky for sharing the pEYFP-C1-mRac1b vector and members of the Kissil and Albelda labs for technical assistance. We thank the Wistar Transgenics and Animal core facilities. This work was supported by Grant CA124495 (JLK).

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  1. C Zhou and S Licciulli: These authors contributed equally to the manuscript

Authors and Affiliations

  1. Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA

    C Zhou, S Licciulli, J L Avila, M Cho, S Troutman, A V Kossenkov, L C Showe, Q Liu & J L Kissil

  2. Cell and Molecular Biology Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    J L Avila & J L Kissil

  3. Animal transgenics core facility, The Wistar Institute, Philadelphia, PA, USA

    P Jiang

  4. Thoracic Oncology Research Laboratory, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    A Vachani & S M Albelda

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  1. C Zhou
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Correspondence to J L Kissil.

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Zhou, C., Licciulli, S., Avila, J. et al. The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis. Oncogene 32, 903–909 (2013). https://doi.org/10.1038/onc.2012.99

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