Overexpression of CCT8 and its significance for tumor cell proliferation, migration and invasion in glioma

Qiu, Xiaojun; He, Xiaojuan; Huang, Qiyu; Liu, Xianchen; Sun, Guan; Guo, Jun; Yuan, Damin; Yang, Lixiang; Ban, Na; Fan, Shaochen; Tao, Tao; Wang, Donglin

doi:10.1016/j.prp.2015.04.012

Cited by 43 publications

(38 citation statements)

References 36 publications

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“…Connecting processes at the PN level, this evidence suggests a connection between TRiC/CCT and HSF1 stress response signalling also in cancers [ 38 , 73 ]. While increased expression of TRiC/CCT subunits has been observed in cancer cell lines [ 74 ], and increases in CCT8 expression are linked to individual cancers [ 75 , 76 ], we describe consistent TRiC/CCT upregulation within global cancer chaperome signatures throughout the majority of TCGA solid cancers, or Group 1 cancers, whereas Group 2 cancers lack chaperome and, to large extent, TRiC/CCT upregulation.…”

Section: Discussionsupporting

confidence: 58%

A systematic atlas of chaperome deregulation topologies across the human cancer landscape

et al. 2018

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Proteome balance is safeguarded by the proteostasis network (PN), an intricately regulated network of conserved processes that evolved to maintain native function of the diverse ensemble of protein species, ensuring cellular and organismal health. Proteostasis imbalances and collapse are implicated in a spectrum of human diseases, from neurodegeneration to cancer. The characteristics of PN disease alterations however have not been assessed in a systematic way. Since the chaperome is among the central components of the PN, we focused on the chaperome in our study by utilizing a curated functional ontology of the human chaperome that we connect in a high-confidence physical protein-protein interaction network. Challenged by the lack of a systems-level understanding of proteostasis alterations in the heterogeneous spectrum of human cancers, we assessed gene expression across more than 10,000 patient biopsies covering 22 solid cancers. We derived a novel customized Meta-PCA dimension reduction approach yielding M-scores as quantitative indicators of disease expression changes to condense the complexity of cancer transcriptomics datasets into quantitative functional network topographies. We confirm upregulation of the HSP90 family and also highlight HSP60s, Prefoldins, HSP100s, ER- and mitochondria-specific chaperones as pan-cancer enriched. Our analysis also reveals a surprisingly consistent strong downregulation of small heat shock proteins (sHSPs) and we stratify two cancer groups based on the preferential upregulation of ATP-dependent chaperones. Strikingly, our analyses highlight similarities between stem cell and cancer proteostasis, and diametrically opposed chaperome deregulation between cancers and neurodegenerative diseases. We developed a web-based Proteostasis Profiler tool (Pro2) enabling intuitive analysis and visual exploration of proteostasis disease alterations using gene expression data. Our study showcases a comprehensive profiling of chaperome shifts in human cancers and sets the stage for a systematic global analysis of PN alterations across the human diseasome towards novel hypotheses for therapeutic network re-adjustment in proteostasis disorders.

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Section: Discussionsupporting

confidence: 58%

A systematic atlas of chaperome deregulation topologies across the human cancer landscape

et al. 2018

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“…Proteasome and chaperone levels in cancer cells are consistent with the special requirements of these cells, such as elimination of aberrant proteins. Interestingly, the expression of CCT8 is increased in gliomas and hepatocellular carcinoma whereas its knockdown induces a decrease in the proliferation and invasion capacity of these cells5354. Similarly, other CCT subunits have been linked to cancer55.…”

Section: Discussionmentioning

confidence: 99%

Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan

et al. 2016

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Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT assembly. Moreover, increased TRiC/CCT complex is required to avoid aggregation of mutant Huntingtin protein. We further show that increased expression of CCT8 in somatic tissues extends Caenorhabditis elegans lifespan in a TRiC/CCT-dependent manner. Ectopic expression of CCT8 also ameliorates the age-associated demise of proteostasis and corrects proteostatic deficiencies in worm models of Huntington's disease. Our results suggest proteostasis is a common principle that links organismal longevity with hESC immortality.

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“…With a large number of substrates representing a broad spectrum of functionalities, CCT is probably involved in many other oncogenesis pathways. It is not surprising that CCT or its subunits have been implicated in the development of various types of cancers, such as breast [ 15 , 22 ], liver [ 17 , 20 , 23 ], colon [ 24 , 25 ], lung cancer [ 26 ] and glioma [ 27 ]. However, little is known regarding the role of CCT3 in the development of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth

Zhang

Han

et al. 2017

Oncotarget

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BackgroundMembers of eukaryotic chaperonin family are essential for cell survival. Dysregulation of Chaperonin containing TCP-1 subunit 3 (CCT3) has been implicated in the development of several types of cancers. However, the role of CCT3 in the development of gastric cancer has yet to be determined.MethodsThe expression patterns of CCT3 in the surgical specimens from 26 gastric cancer patients were evaluated using immunohistochemistry methods. To study the possible roles of CCT3 in the growth and survival of gastric cancer cells, RNA interference was used to knockdown CCT3 expression in gastric cancer cell lines BGC-823 and MGC-803. The effects of CCT3 knockdown on cancer cell proliferation, apoptosis and in vivo growth were examined. Finally, gene expression changes related to CCT3 knockdown were studied using gene array analysis and western blotting.ResultsHigher level of CCT3 expression was detected in the gastric cancer tissue compared to adjacent non-cancerous epithelium. Knockdown of CCT3 inhibited proliferation and colony formation while promoted apoptosis of gastric cancer cells in vitro. Gastric cancer cells exhibited lower growth potential in nude mice when CCT3 expression was suppressed. Gene expression analysis showed that CCT3 knockdown was associated with down-regulation of mitogen-activated protein kinase kinase kinase 7, cell division cycle 42, cyclin D3 and up-regulation of cyclin-dependent kinase 2 and 6.ConclusionOur results suggested that CCT3 played a critical role in gastric cancer growth and survival. Further studies on the mechanisms of CCT3 function is mandated to develop novel cancer treatment targeting CCT3.

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Overexpression of CCT8 and its significance for tumor cell proliferation, migration and invasion in glioma

Cited by 43 publications

References 36 publications

A systematic atlas of chaperome deregulation topologies across the human cancer landscape

A systematic atlas of chaperome deregulation topologies across the human cancer landscape

Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan

Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth

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