Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Jumonji domain-containing protein 6 (JMJD6) is a non-heme Fe(II) 2-oxoglutarate (2OG)-dependent oxygenase with arginine demethylase and lysyl hydroxylase activities. Its initial discovery as a dispensable phosphatidylserine receptor (PSR) in the cell membrane of macrophages for phagocytosis was squashed by newer studies which revealed its nuclear localization and bifunctional enzymatic activity. Though its interaction with several nuclear and cytoplasmic target proteins has been demonstrated, the exact mechanisms and clinical significance of these various biologic interplays are not yet well established. Recent investigations have shed the light on the multiple pathways by which JMJD6 can regulate cell proliferation and cause tumorigenesis. Clinically, JMJD6 has been associated with more aggressive and metastatic disease, poorer prognosis, and lower overall survival rates-particularly in lung colon and oral cancers. JMJD6 is a novel biomarker for predicting future disease outcomes and is a target for new therapeutic treatments in future studies. Aberrant expression and dysregulation of JMJD6 are implicated in various other processes such as impaired T-cell proliferation and maturation, inoculation, and virulence of foot-and-mouth disease virus (FMDV), and impaired methylation of innate immunity factor. This article reviews the association of JMJD6 with various pathological processes-particularly, its role in tumorigenesis and virological interactions.
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PMID:Bifunctional Enzyme JMJD6 Contributes to Multiple Disease Pathogenesis: New Twist on the Old Story. 2858 76

Metastasis associates with late stages of lung cancer progression and remains the main cause of patient death due to the lack of clinically effective therapeutics. Here we report that the transcription factor GATA3 and its co-factor FOG2 commonly promote the expression of the lysyl hydroxylase (LH) family members, including LH2 and LH3, which in turn drive lung adenocarcinoma cell migration, invasion, and metastasis. We show evidence that both LH2 and LH3 are direct transcription targets for GATA3. Knockdown of either LH2 or LH3 suppresses migration and invasion; on the contrary, forced expression of LH2 or LH3 promotes growth and migration, suggesting that the two LHs exert redundant oncogenic functions. Importantly, re-expression of LH2 is sufficient to restore the metastatic capacity of GATA3-depleted cells, suggesting a role for LHs as the downstream mediators of GATA3. Collectively, our data reveal a pro-metastatic GATA3-LHs axis for lung cancer, supporting the notion that targeting LHs may be useful for treating lung cancer.
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PMID:Lysyl hydroxylases are transcription targets for GATA3 driving lung cancer cell metastasis. 3009 26