CCT3 acts upstream of YAP and TFCP2 as a potential target and tumour biomarker in liver cancer
| العنوان: | CCT3 acts upstream of YAP and TFCP2 as a potential target and tumour biomarker in liver cancer |
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| المؤلفون: | Jiayi Wang, Susu Guo, Jiafei Lin, Ya Liu, Fenyong Sun, Yuxin Chen, Yongxia Qiao, Xiao Zhang, Qiuhui Pan, Guoqing Zhu, Yueyue Yang |
| المصدر: | Cell Death and Disease, Vol 10, Iss 9, Pp 1-15 (2019) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Protein subunit, Transcriptional regulatory elements, Immunology, Mice, Nude, Article, Tumour biomarkers, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, 0302 clinical medicine, Ubiquitin, Cell Line, Tumor, medicine, Biomarkers, Tumor, Animals, Humans, lcsh:QH573-671, Adaptor Proteins, Signal Transducing, biology, Chemistry, Protein Stability, lcsh:Cytology, Binding protein, Liver Neoplasms, Ubiquitination, RNA-Binding Proteins, YAP-Signaling Proteins, Cell Biology, medicine.disease, Prognosis, Phenotype, Biomarker (cell), Ubiquitin ligase, Up-Regulation, DNA-Binding Proteins, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, TFCP2, Heterografts, Liver cancer, Chaperonin Containing TCP-1, Transcription Factors |
| الوصف: | Although Yes-associated protein (YAP) is very important to liver cancer, its nuclear localisation prevents consideration as a promising therapeutic target and a diagnostic biomarker. Recently, we reported that the protumourigenic roles of YAP in liver cancer are indispensable for transcription factor CP2 (TFCP2) in a Hippo-independent manner; however, proteins that act upstream to simultaneously control YAP and TFCP2 remain unclear. The aim of this study was to uncover such proteins and evaluate whether they are potential YAP-associated therapeutic targets and diagnostic biomarkers. Mass spectrometry revealed that chaperonin containing TCP1 subunit 3 (CCT3) co-interact with YAP and TFCP2, and notably, CCT3 is a non-nuclear protein. CCT3 was elevated in liver cancer, and its higher expression was associated with poorer overall survival. Inhibiting CCT3 resulted in a suppressed transformative phenotype in liver cancer cells, suggesting that CCT3 might be a potential therapeutic target. CCT3 prolonged half-life of YAP and TFCP2 by blocking their ubiquitination caused by poly(rC) binding protein 2 (PCBP2) in a beta-transducin repeat containing E3 ubiquitin protein ligase (βTrCP)-independent manner. Interestingly, PCBP2 directly interacted with YAP via a WB motif-WW domain interaction, whereas indirectly interacted with TFCP2 via the aid of YAP. Furthermore, CCT3 was capable of separating PCBP2-YAP interactions, thereby preventing YAP and TFCP2 from PCBP2-induced ubiquitination. Moreover, YAP and TFCP2 were downstream of CCT3 to positively control tumourigenesis, yet such effects were inhibited by PCBP2. Clinically, CCT3 was positively correlated with YAP and TFCP2, and elevated levels of the CCT3-YAP-TFCP2 axis might be critical for liver malignancy. In addition, seral-CCT3 was proven to be a potential biomarker, and its diagnostic capacity was better than that of alpha fetoprotein (AFP) to a certain extent. Together, CCT3 acts as a trigger of YAP and TFCP2 to affect tumourigenesis and serves as a potential therapeutic target and biomarker in liver cancer. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0cae38fc1474a6ff4957c3c90369b076Test http://link.springer.com/article/10.1038/s41419-019-1894-5Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0cae38fc1474a6ff4957c3c90369b076 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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