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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This work was supported by grants from the NIH (HL56745 and CA90578) to DGT.
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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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DOI: https://doi.org/10.1038/onc.2011.57
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