title: Tribbles breaking bad: TRIB2 suppresses FOXO and acts as an oncogenic protein in melanoma.
abstract: TRIB2 (tribbles homolog 2) encodes one of three members of the tribbles family in mammals. These members share a Trb (tribbles) domain, which is homologous to protein serine-threonine kinases, but lack the active site lysine. The tribbles proteins interact and modulate the activity of signal transduction pathways in a number of physiological and pathological processes. TRIB2 has been identified as an oncogene that inactivates the transcription factor CCAAT/enhancer-binding protein α (C/EBPα) and causes acute myelogenous leukaemia (AML). Recent research provided compelling evidence that TRIB2 can also act as oncogenic driver in solid tumours, such as lung and liver cancer. In particular, our recent work demonstrated that TRIB2 is dramatically overexpressed in malignant melanomas compared with normal skin and promotes the malignant phenotype of melanoma cells via the down-regulation of FOXO (forkhead box protein O) tumour suppressor activity in vitro and in vivo. TRIB2 was found to be expressed in normal skin, but its expression consistently increased in benign nevi, melanoma and was highest in samples from patients with malignant melanoma. The observation that TRIB2 strongly correlates with the progression of melanocyte-derived malignancies suggests TRIB2 as a meaningful biomarker to both diagnose and stage melanoma. In addition, interfering with TRIB2 activity might be a therapeutic strategy for the treatment of several different tumour types.
authors.affiliation: Centre for Biomedical Research (CBMR), University of Algarve, Campus of Gambelas, 8005-139 Faro, Portugal Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Link
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human
keywords: FOXO (forkhead box protein O); TRIB2 (tribbles homolog 2); biomarker; melanoma; phosphoinositide 3-kinase (PI3K); tribbles