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Overexpression of TRIB2 in human lung cancers contributes to tumorigenesis through downregulation of C/EBPα

Oncogene volume 30, pages 3328–3335 (2011)Cite this article

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Abstract

Lung cancer is the most common cause of cancer-related mortality worldwide. Here, we report elevated expression of tribbles homolog 2 (TRIB2) in primary human lung tumors and in non-small cell lung cancer cells that express low levels of differentiation-inducing transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα). In approximately 10–20% of cases, elevated TRIB2 expression resulted from gene amplification. TRIB2 knockdown was found to inhibit cell proliferation and in vivo tumor growth. In addition, TRIB2 knockdown led to morphological changes similar to C/EBPα overexpression and correlated with increased expression and activity of C/EBPα. TRIB2-mediated regulation of C/EBPα was found to occur through the association of TRIB2 with the E3 ligase TRIM21. Together, these data identify TRIB2 as a potential driver of lung tumorigenesis through a mechanism that involves downregulation of C/EBPα.

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Acknowledgements

This work was supported by grants from the NIH (HL56745 and CA90578) to DGT.

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Author notes

  1. V A Reddy

    Present address: Current address: Sanofi-Aventis US, 270 Albany St, Cambridge, MA, USA.,

  2. K B Grandinetti and T A Stevens: These authors contributed equally to this work.

Authors and Affiliations

  1. Genomics Institute of the Novartis Research Foundation, San Diego, CA, USA

    K B Grandinetti, T A Stevens, S Ha, R J Salamone, J R Walker, J Zhang, S Agarwalla, E C Peters & V A Reddy

  2. Scripps Research Institute, San Diego, CA, USA

    K B Grandinetti

  3. Cancer Science Institute, National University of Singapore,

    D G Tenen

  4. Harvard Stem Cell Institute, Center for Life Sciences, Boston, MA, USA

    D G Tenen

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  1. K B Grandinetti
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Correspondence to K B Grandinetti.

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Grandinetti, K., Stevens, T., Ha, S. et al. Overexpression of TRIB2 in human lung cancers contributes to tumorigenesis through downregulation of C/EBPα. Oncogene 30, 3328–3335 (2011). https://doi.org/10.1038/onc.2011.57

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