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Esophageal squamous cell carcinoma (ESCC) is the ninth largest cause of cancer-related deaths worldwide, with more than 515,000 new cases each year.
, China has the highest incidence and mortality rate of ESCC, at 70%.
ESCC has a poor five-year survival rate due to a lack of early diagnosis, limited treatment options and frequent recurrence of the disease.
, it is urgent to explore the molecular mechanisms associated with the development of ESCC tumors and to identify molecular markers for diagnosing or predicting patient prognosis.
DHODH (dihydro lactic acid dehydrogenase) is a speed-limiting enzyme in the UMP (urealic acid) biosynthetic pathway, and previous studies have shown that in various types of malignant tumors, the expression level of DHODH increases, and its tumor-promoting effect is considered to be related to its synthesized function.
study on the relationship between DHODH over-expression and adverse prognostication in ESCC patients revealed a potential mechanism for DHODH to regulate the β-catenin signal transducting path in ESCC.
researchers found that DHODH binds directly to the N end of β-catenin, disrupting the interaction between GSK3 beta and β-catenin, inhibiting the degradation of β-catenin and promoting the accumulation of β-catenin in the nuclei of cells, eventually leading to activation of the downstream gene, including CCND1, E2F3, Nanog, and OCT4 β
further studies have shown that the regulatory action of DHODH on β-catenin is independent of the catalytic activity of DHODH.
single-factor and multi-factor analysis suggests that the level of expression of DHODH may be an independent prognostic factor in ESCC patients.
DHODH promotes tumor development in general, the results reveal the key role of the β-catenin signal transduction path of DHODH mediated, suggesting that DHODH may act as a versatile switch that can catalyz the metabolism of sorine and regulate tumor-related signaling path paths in ESCC.
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