Expression of activator proteins of SHH/GLI and PI3K/Akt/mTORC1 signaling pathways in human gliomas are associated with high grade tumors

Author(s):  
Julián Henao-Restrepo ◽  
Yudys Anggelly Caro-Urrego ◽  
Lina Marcela Barrera-Arenas ◽  
Juan Carlos Arango-Viana ◽  
Maria Bermudez-Munoz
2019 ◽  
Vol 79 (2) ◽  
pp. 184-193 ◽  
Author(s):  
Dolors Pi Castro ◽  
Roberto José-López ◽  
Francisco Fernández Flores ◽  
Rosa M Rabanal Prados ◽  
Maria Teresa Mandara ◽  
...  

Abstract Dogs develop gliomas with similar histopathological features to human gliomas and share with them the limited success of current therapeutic regimens such as surgery and radiation. The tumor microenvironment in gliomas is influenced by immune cell infiltrates. The present study aims to immunohistochemically characterize the tumor-infiltrating lymphocyte (TIL) population of naturally occurring canine gliomas, focusing on the expression of Forkhead box P3-positive (FOXP3+) regulatory T-cells (Tregs). Forty-three canine gliomas were evaluated immunohistochemically for the presence of CD3+, FOXP3+, and CD20+ TILs. In low-grade gliomas, CD3+ TILs were found exclusively within the tumor tissue. In high-grade gliomas, they were present in significantly higher numbers throughout the tumor and in the brain-tumor junction. CD20+ TILs were rarely found in comparison to CD3+ TILs. FOXP3+ TILs shared a similar distribution with CD3+ TILs. The accumulation of FOXP3+ Tregs within the tumor was more pronounced in astrocytic gliomas than in tumors of oligodendroglial lineage and the difference in expression was significant when comparing low-grade oligodendrogliomas and high-grade astrocytomas. Only high-grade astrocytomas presented FOXP3+ cells with tumoral morphology. In spontaneous canine gliomas, TILs display similar characteristics (density and distribution) as described for human gliomas, supporting the use of the dog as an animal model for translational immunotherapeutic studies.


2015 ◽  
Author(s):  
Jillian M. Silva ◽  
Marian M. Deuker ◽  
Wayne R. Joseph ◽  
Bruce C. Baguley ◽  
Martin McMahon

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1419
Author(s):  
Cheng-Shuo Huang ◽  
Jar-Yi Ho ◽  
Jung-Hwa Chiang ◽  
Cheng-Ping Yu ◽  
Dah-Shyong Yu

Exosomes are essential for several tumor progression-related processes, including the epithelial–mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) comprise a major group of exosomal components and regulate the neoplastic development of several cancer types; however, the progressive role of exosomal lncRNAs in bladder cancer have rarely been addressed. In this study, we identified two potential aggressiveness-promoting exosomal lncRNAs, LINC00960 and LINC02470. Exosomes derived from high-grade bladder cancer cells enhanced the viability, migration, invasion and clonogenicity of recipient low-grade bladder cancer cells and activated major EMT-upstream signaling pathways, including β-catenin signaling, Notch signaling, and Smad2/3 signaling pathways. Nevertheless, LINC00960 and LINC02470 were expressed at significantly higher levels in T24 and J82 cells and their secreted exosomes than in TSGH-8301 cells. Moreover, exosomes derived from LINC00960 knockdown or LINC02470 knockdown T24 cells significantly attenuated the ability of exosomes to promote cell aggressiveness and activate EMT-related signaling pathways in recipient TSGH-8301 cells. Our findings indicate that exosome-derived LINC00960 and LINC02470 from high-grade bladder cancer cells promote the malignant behaviors of recipient low-grade bladder cancer cells and induce EMT by upregulating β-catenin signaling, Notch signaling, and Smad2/3 signaling. Both lncRNAs may serve as potential liquid biomarkers for the prognostic surveillance of bladder cancer progression.


Cell Reports ◽  
2019 ◽  
Vol 26 (11) ◽  
pp. 3037-3050.e4 ◽  
Author(s):  
Chuan-Ming Xie ◽  
Mingjia Tan ◽  
Xiao-Tong Lin ◽  
Di Wu ◽  
Yihan Jiang ◽  
...  

2018 ◽  
Vol 11 (559) ◽  
pp. eaav3530 ◽  
Author(s):  
Sascha Martens

In human cells, the p62 protein acts as an adaptor in various signaling pathways as well as a receptor for selective autophagy. In this issue ofScience Signaling, Sanchez-Garridoet al. show that proteolytic cleavage of p62 by caspase-8 determines whether p62 functions as an mTORC1 signaling adaptor or autophagy receptor.


2017 ◽  
Vol 75 (5) ◽  
pp. 871-887 ◽  
Author(s):  
Michaël H. Meel ◽  
Sophie A. Schaper ◽  
Gertjan J. L. Kaspers ◽  
Esther Hulleman

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