Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Succinate is an important intermediate of the tricarboxylic acid cycle. Recently discovered roles of succinate demonstrate its involvement in immunity and cancer biology; however, the precise underlying mechanisms of its involvement in these additional roles remain to be determined. In the present study, succinate dehydrogenase (SDH) B was decreased in uterine endometrial cancer cells (UECC) under negative regulation of estrogen. This decrease was the result of lower expression levels of ubiquitin C (UBC), which was associated with the activation of peroxisome proliferator-activated receptor gamma and specificity protein 1. The decreased levels of SDHB resulted in the accumulation of succinate in UECC, and thus, a decrease in the production of fumaric acid. Succinate downregulated voltage-gated potassium channel subfamily Q member 1 (KCNQ1) levels by activating serum/glucocorticoid regulated kinase 1 and promoted the growth of UECC in vitro and in vivo. Treatment with melatonin restricted estrogen/UBC/SDHB-induced succinate accumulation and upregulated expression of KCNQ1 and reduced the succinate-mediated growth of UECC in vitro and in vivo. Furthermore, overexpression of melatonin receptor 1B amplified the inhibitory effects of melatonin on succinate-mediated UECC growth. Together, the data in the present study suggest that melatonin suppresses UECC progression by inhibiting estrogen/UBC/SDHB-induced succinate accumulation. The present study provides a scientific basis for potential therapeutic strategies and targets in UEC, particularly for patients with abnormally low levels of SDHB.
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PMID:Melatonin alleviates progression of uterine endometrial cancer by suppressing estrogen/ubiquitin C/SDHB-mediated succinate accumulation. 3206 49