Musashi1 regulates survival of hepatoma cell lines by activation of Wnt signalling pathway

2014 ◽  
Vol 35 (3) ◽  
pp. 986-998 ◽  
Author(s):  
Kunlun Chen ◽  
Qing Gao ◽  
Wei Zhang ◽  
Zhongwei Liu ◽  
Jiangyi Cai ◽  
...  
2008 ◽  
Vol 416 (2) ◽  
pp. 211-218 ◽  
Author(s):  
Sasha H. Anagnostou ◽  
Peter R. Shepherd

The canonical Wnt signalling pathway acts by slowing the rate of ubiquitin-mediated β-catenin degradation. This results in the accumulation and subsequent nuclear translocation of β-catenin, which induces the expression of a number of genes involved in growth, differentiation and metabolism. The mechanisms regulating the Wnt signalling pathway in the physiological context is still not fully understood. In the present study we provide evidence that changes in glucose levels within the physiological range can acutely regulate the levels of β-catenin in two macrophage cell lines (J774.2 and RAW264.7 cells). In particular we find that glucose induces these effects by promoting an autocrine activation of Wnt signalling that is mediated by the hexosamine pathway and changes in N-linked glycosylation of proteins. These studies reveal that the Wnt/β-catenin system is a glucose-responsive signalling system and as such is likely to play a role in pathways involved in sensing changes in metabolic status.


2018 ◽  
Author(s):  
Svetlana Myssina ◽  
John Clark-Corrigall ◽  
Martin Michaelis ◽  
Jindrich Cinatl ◽  
Shafiq U. Ahmed ◽  
...  

AbstractNeuroblastoma (NB) is the most common paediatric solid cancer with high fatality, relapses and acquired resistance to drug therapy. The clinical challenge NB poses requires new therapeutic approaches to improve survival rates.The WNT signalling pathway is crucial in embryonic development but has also been reported to be dysregulated in glioblastoma, ovarian, breast and colorectal cancer. LGR5 is a receptor which potentiates the WNT/β-catenin signalling pathway, hence contributing to cancer stem cell proliferation and self-renewal. LGR5 has been reported to promote both development and survival of colorectal cancer and glioblastomas.Our previous study illustrated that LGR5 is associated with aggressiveness in NB cell lines established at different stages of treatment. Following these findings, we investigated whether LGR5 is involved in acquired drug resistance via the WNT pathway in NB cell lines.Cell lines in this study have an acquired drug resistance to vincristine (VCR) or doxorubicin (DOX).In this study, we showed LGR5-LRP6 cooperation with enhanced expression of both proteins in SHSY5YrVCR, IMR32rDOX, IMR5rVCR and IMR5rDOX NB cell lines compared to paired parental cells. We also found elevated expression of β-catenin in cell lines with acquired drug resistance is indicative of β-catenin-dependent WNT signalling.This study warrants further investigation into the role of the WNT signalling pathway in acquired drug resistance.


2020 ◽  
Vol 9 (2) ◽  
pp. 323
Author(s):  
Young-Sun Lee ◽  
Eunjung Ko ◽  
Eileen L. Yoon ◽  
Young Kul Jung ◽  
Ji Hoon Kim ◽  
...  

Alpha fetoprotein (AFP) has been used as a serologic indicator of hepatocellular carcinoma (HCC). We aimed to identify an HCC-specific serum biomarker for diagnosis using a multiplexed proteomic technique in HCC patients with normal AFP levels. A total of 152 patients were included from Guro Hospital, Korea University. Among 267 identified proteins, 28 and 86 proteins showed at least a two-fold elevation or reduction in expression, respectively. Multiple reaction monitoring (MRM) analysis of 41 proteins revealed 10 proteins were differentially expressed in patients with liver cirrhosis and HCC patients with normal AFP. A combination of tripartite motif22 (Trim22), seprase, and bone morphogenetic protein1 had an area under receiver operating characteristic of 0.957 for HCC diagnosis. Real-time PCR and western blot analysis of the paired tumor/non-tumor liver tissue in HCC revealed a reduced expression of Trim22 in the tumor tissue. Also, serum levels of Trim22 were significantly reduced in HCC patients with normal AFP compared to those with liver cirrhosis (p = 0.032). Inhibition of Trim22 increased cellular proliferation in human hepatoma cell lines, whereas overexpression of Trim22 decreased cellular proliferation in hepatoma cell lines. In conclusion, the combination of three serum markers improved the chance of diagnosing HCC. MRM-based quantification of the serum protein in patients with normal AFP provides the potential for early diagnosis of HCC.


PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160843 ◽  
Author(s):  
Nicole Lange ◽  
Armelle Tsamo Tontsa ◽  
Claudia Wegscheid ◽  
Pierre Mkounga ◽  
Augustin Ephrem Nkengfack ◽  
...  

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