RACO-1 modulates Hippo signalling in oesophageal squamous cell carcinoma.
Dan PangWeilong WangXiaofeng ZhouKui LuJinghang ZhangZhiguo ChenLingchao WangFangfang ShenZhen ChenSujie WangJinghan HouAijia ZhangBenjie LvCan GaoZiyi YanYuhan HuTingmin ChangLidong WangXiumin LiPublished in: Journal of cellular and molecular medicine (2020)
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.
Keyphrases
- squamous cell carcinoma
- papillary thyroid
- end stage renal disease
- newly diagnosed
- chronic kidney disease
- single cell
- poor prognosis
- small molecule
- copy number
- binding protein
- squamous cell
- ejection fraction
- transcription factor
- induced apoptosis
- gene expression
- signaling pathway
- machine learning
- prognostic factors
- young adults
- locally advanced
- electronic health record
- cell death
- radiation therapy
- patient reported
- genome wide identification
- polycyclic aromatic hydrocarbons