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首页> 外文期刊>Cellular Signalling >MLL2 promotes cancer cell lymph node metastasis by interacting with RelA and facilitating STC1 transcription
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MLL2 promotes cancer cell lymph node metastasis by interacting with RelA and facilitating STC1 transcription

机译：通过与Rela相互作用并促进STC1转录，MLL2促进癌细胞淋巴结转移

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Esophageal squamous cell carcinoma (ESCC) presents with lymph node metastasis in the early stages, limiting the opportunities for curative local resection, including endoscopic submucosal dissection (ESD). ESD is regarded as the standard treatment for early-stage ESCCs. However, radical surgery is recommended when lymph node metastasis risk exists. More efforts are needed to find the markers for early prediction and clarify the molecular mechanism underlying the pathogenesis of lymph node metastasis. Recently, aberrant regulation of gene expression by histone methylation modifiers has emerged as an important mechanism for cancer metastasis. Herein, we demonstrated that mixed-lineage leukemia 2 (MLL2) positively regulates gene expression programs associated with ESCC cell migration. MLL2 interacts with RelA in the nucleus to enhance transcription of stanniocalcin-1 (STC1) and to facilitate cancer metastasis. Meanwhile, MLL2 knockdown resulted in a significant decrease in the migration of ESCC cells. Clinically, high level of MLL2 was significantly associated with early-stage ESCC lymph node metastasis. In summary, these findings discovered a previously unidentified molecular pathway underlying the coordinated regulation of metastasis-related STC-1 expression by MLL2 and RelA and highlighted the critical role of MLL2 in ESCC.
机译：食管鳞状细胞癌（ESCC）在早期阶段的淋巴结转移呈现，限制了治疗局部切除的机会，包括内窥镜粘膜粘膜释放（ESD）。 ESD被视为早期ESCCS的标准治疗。然而，当存在淋巴结转移风险时建议使用自由基手术。需要更多的努力来查找早期预测的标志物，并阐明淋巴结转移发病机制的分子机制。最近，通过组蛋白甲基化改性剂的基因表达的异常调节作为癌症转移的重要机制。在此，我们证明了混合谱系白血病2（MLL2）正征与ESCC细胞迁移相关的基因表达程序。 MLL2与细胞核中的Rela相互作用，以增强甾烷-1（STC1）的转录，并促进癌症转移。同时，MLL2敲低导致ESCC细胞迁移的显着降低。临床上，高水平的MLL2与早期ESCC淋巴结转移显着相关。总之，这些发现发现了先前未识别的分子途径，以通过MLL2和Rela进行转移相关的STC-1表达的协调调节，并突出显示MLL2在ESCC中的关键作用。

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