scholarly journals Shedding light on an old mystery: Thalidomide suppresses survival pathways to induce limb defects

Cell Cycle ◽  
2008 ◽  
Vol 7 (9) ◽  
pp. 1121-1127 ◽  
Author(s):  
Jürgen Knobloch ◽  
Ulrich Rüther
Keyword(s):  
Limb Defects ◽  
Survival Pathways

scholarly journals CSIG-03. RECONCILING TUMOR HETEROGENEITY IN GLIOBLASTOMA USING A PATHWAY-BASED APPROACH

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii28-ii28
Author(s):  
Alvaro Alvarado ◽  
Kaleab Tessema ◽  
Kunal Patel ◽  
Riki Kawaguchi ◽  
Richard Everson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Patient Survival ◽  
Molecular Subtype ◽  
Gene List ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Molecular Architecture ◽  
Survival Pathways ◽  
Cancer Genome Atlas

Abstract Despite efforts to gain a deeper understanding of its molecular architecture, glioblastoma (GBM) remains uniformly fatal. While genome-based molecular subtyping has revealed that GBMs may be parsed into several molecularly distinct categories, this insight has yielded little progress towards extending patient survival. In particular, the great phenotypic heterogeneity of GBM – both inter and intratumorally – has hindered therapeutic efforts. To this end, we interrogated tumor samples using a pathway-based approach to resolve tumoral heterogeneity. Gene set enrichment analysis (GSEA) was applied to gene expression data and used to provide an overview of each sample that can be compared to other samples by generating sample clusters based on overall patterns of enrichment. The Cancer Genome Atlas (TCGA) samples were clustered using the canonical and oncogenic signatures and in both cases the clustering was distinct from the molecular subtype previously reported and clusters were informative of patient survival. We also analyzed single cell RNA sequencing datasets and uniformly found two clusters of cells enriched for cell cycle regulation and survival pathways. We have validated our approach by generating gene lists from common elements found in the top contributing genesets for a particular cluster and testing the top targets in appropriate gliomasphere patient-derived lines. Samples enriched for cell cycle related genesets showed a decrease in sphere formation capacity when E2F1, out top target, was silenced and when treated with fulvestrant and calcitriol, which were identified as potential drugs targeting this genelist. Conversely, no changes were observed in samples not enriched for this gene list. Finally, we interrogated spatial heterogeneity and found higher enrichment of the proliferative signature in contrast enhancing compared with non-enhancing regions. Our studies relate inter- and intratumoral heterogeneity to critical cellular pathways dysregulated in GBM, with the ultimate goal of establishing a pipeline for patient- and tumor-specific precision medicine.

Tea bioactive components prevent carcinogenesis via anti‐pathogen, anti‐inflammation and cell survival pathways

IUBMB Life ◽  
2020 ◽  
Author(s):  
Xiangqi Fan ◽  
Xiangjun Xiao ◽  
Xiangbing Mao ◽  
Daiwen Chen ◽  
Bing Yu ◽  
...  
Keyword(s):  
Cell Survival ◽  
Bioactive Components ◽  
Survival Pathways ◽  
Anti Inflammation

scholarly journals Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

2021 ◽  
Vol 22 (9) ◽  
pp. 4716
Author(s):  
Francesco Ciscato ◽  
Lavinia Ferrone ◽  
Ionica Masgras ◽  
Claudio Laquatra ◽  
Andrea Rasola
Keyword(s):  
Endoplasmic Reticulum ◽  
Aerobic Glycolysis ◽  
Neoplastic Progression ◽  
Malignant Growth ◽  
Hexokinase 2 ◽  
Genetic Ablation ◽  
Contact Points ◽  
Survival Pathways ◽  
The Family ◽  
Definition Of

Hexokinases are a family of ubiquitous exose-phosphorylating enzymes that prime glucose for intracellular utilization. Hexokinase 2 (HK2) is the most active isozyme of the family, mainly expressed in insulin-sensitive tissues. HK2 induction in most neoplastic cells contributes to their metabolic rewiring towards aerobic glycolysis, and its genetic ablation inhibits malignant growth in mouse models. HK2 can dock to mitochondria, where it performs additional functions in autophagy regulation and cell death inhibition that are independent of its enzymatic activity. The recent definition of HK2 localization to contact points between mitochondria and endoplasmic reticulum called Mitochondria Associated Membranes (MAMs) has unveiled a novel HK2 role in regulating intracellular Ca2+ fluxes. Here, we propose that HK2 localization in MAMs of tumor cells is key in sustaining neoplastic progression, as it acts as an intersection node between metabolic and survival pathways. Disrupting these functions by targeting HK2 subcellular localization can constitute a promising anti-tumor strategy.

scholarly journals Metformin Dysregulates the Unfolded Protein Response and the WNT/β-Catenin Pathway in Endometrial Cancer Cells through an AMPK-Independent Mechanism

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1067
Author(s):  
Domenico Conza ◽  
Paola Mirra ◽  
Gaetano Calì ◽  
Luigi Insabato ◽  
Francesca Fiory ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Independent Manner ◽  
Growth And Survival ◽  
Unfolded Protein ◽  
Compound C ◽  
Survival Pathways ◽  
The Unfolded Protein Response ◽  
Protein Response

Multiple lines of evidence suggest that metformin, an antidiabetic drug, exerts anti-tumorigenic effects in different types of cancer. Metformin has been reported to affect cancer cells’ metabolism and proliferation mainly through the activation of AMP-activated protein kinase (AMPK). Here, we show that metformin inhibits, indeed, endometrial cancer cells’ growth and induces apoptosis. More importantly, we report that metformin affects two important pro-survival pathways, such as the Unfolded Protein Response (UPR), following endoplasmic reticulum stress, and the WNT/β-catenin pathway. GRP78, a key protein in the pro-survival arm of the UPR, was indeed downregulated, while GADD153/CHOP, a transcription factor that mediates the pro-apoptotic response of the UPR, was upregulated at both the mRNA and protein level. Furthermore, metformin dramatically inhibited β-catenin mRNA and protein expression. This was paralleled by a reduction in β-catenin transcriptional activity, since metformin inhibited the activity of a TCF/LEF-luciferase promoter. Intriguingly, compound C, a well-known inhibitor of AMPK, was unable to prevent all these effects, suggesting that metformin might inhibit endometrial cancer cells’ growth and survival through the modulation of specific branches of the UPR and the inhibition of the Wnt/β-catenin pathway in an AMPK-independent manner. Our findings may provide new insights on the mechanisms of action of metformin and refine the use of this drug in the treatment of endometrial cancer.

A rare case of mandibular cleft with limb defects

2015 ◽  
Vol 64 ◽  
pp. S55-S56
Author(s):  
A. Sharma ◽  
S. Kochhar ◽  
A. Huria
Keyword(s):  
Rare Case ◽  
Limb Defects

A Multivariate Analysis of the Risk Indicators of Reduction Limb Defects

1984 ◽  
Vol 13 (4) ◽  
pp. 459-464 ◽  
Author(s):  
TIMO ARO ◽  
JAASON HAAPAKOSKI ◽  
OLLI P HEINONEN
Keyword(s):  
Multivariate Analysis ◽  
Risk Indicators ◽  
Limb Defects

scholarly journals WNT1-inducible signaling pathway protein-1 activates diverse cell survival pathways and blocks doxorubicin-induced cardiomyocyte death

2010 ◽  
Vol 22 (5) ◽  
pp. 809-820 ◽  
Author(s):  
Balachandar Venkatesan ◽  
Sumanth D. Prabhu ◽  
Kaliyamurthi Venkatachalam ◽  
Srinivas Mummidi ◽  
Anthony J. Valente ◽  
...  
Keyword(s):  
Cell Survival ◽  
Signaling Pathway ◽  
Survival Pathways

Effect of 2-Hydroxyethyl Methacrylate on Human Pulp Cell Survival Pathways ERK and AKT

2008 ◽  
Vol 34 (6) ◽  
pp. 684-688 ◽  
Author(s):  
Gianrico Spagnuolo ◽  
Vincenzo D'Antò ◽  
Rosa Valletta ◽  
Caterina Strisciuglio ◽  
Gottfried Schmalz ◽  
...  
Keyword(s):  
Cell Survival ◽  
Hydroxyethyl Methacrylate ◽  
Pulp Cell ◽  
Survival Pathways
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