Oesophageal cancer is one of the most lethal malignancies worldwide, whereas the 5‐year survival is less than 20%. Although the detailed carcinogenic mechanisms are not totally clear, recent genomic sequencing data showed dysregulation of Hippo signalling could be a critical factor for oesophageal squamous cell carcinoma (ESCC) progression. Therefore, understanding of the molecular mechanisms that control Hippo signalling activity is of great importance to improve ESCC diagnostics and therapeutics. Our current study revealed RACO‐1 as an inhibitory protein for YAP/TEAD axis. Depletion of RACO‐1 increases the protein level of YAP and expression of YAP/TEAD target gene. Besides, RACO‐1 silencing could promote ESCC cell invasion and migration, which effect could be rescued by YAP depletion in ESCC cells. Immunoprecipitation showed that RACO‐1 associated with YAP and promote ubiquitination and degradation of YAP at k48 poly‐ubiquitination site. Our research discovered a new regulator of Hippo signalling via modulating YAP stability. RACO‐1 could be a promising factor, which serves cancer diagnostics and therapeutics in ESCC patients.

中文翻译：

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RACO-1调节食管鳞状细胞癌中的Hippo信号传导。

食道癌是全球最致命的恶性肿瘤之一，而5年生存率不到20％。尽管详细的致癌机制尚不完全清楚，但最近的基因组测序数据表明，Hippo信号传导异常可能是食管鳞状细胞癌（ESCC）进展的关键因素。因此，了解控制Hippo信号传导活性的分子机制对于改善ESCC诊断和治疗非常重要。我们目前的研究表明RACO-1是YAP / TEAD轴的抑制蛋白。RACO-1的减少会增加YAP的蛋白质水平和YAP / TEAD靶基因的表达。此外，RACO-1沉默可以促进ESCC细胞的侵袭和迁移，而通过在ESCC细胞中消耗YAP可以挽救这种效应。免疫沉淀显示RACO-1与YAP相关，并在k48多泛素化位点促进YAP的泛素化和降解。我们的研究通过调节YAP稳定性发现了一种新的Hippo信号调节剂。RACO-1可能是一个有前途的因素，可为ESCC患者进行癌症诊断和治疗。