scholarly journals AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress

Nature ◽  
2012 ◽  
Vol 485 (7400) ◽  
pp. 661-665 ◽  
Author(s):  
Sang-Min Jeon ◽  
Navdeep S. Chandel ◽  
Nissim Hay
Keyword(s):  
Cell Survival ◽  
Tumour Cell ◽  
Energy Stress

Mitochondrial elongation-mediated glucose metabolism reprogramming is essential for tumour cell survival during energy stress

Oncogene ◽  
2017 ◽  
Vol 36 (34) ◽  
pp. 4901-4912 ◽  
Author(s):  
J Li ◽  
Q Huang ◽  
X Long ◽  
X Guo ◽  
X Sun ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Cell Survival ◽  
Tumour Cell ◽  
Energy Stress ◽  
Mitochondrial Elongation

The warburg effect and tumour cell survival in human GBMs

2007 ◽  
Vol 30 (4) ◽  
pp. 97 ◽  
Author(s):  
A Wolf ◽  
J Mukherjee ◽  
A Guha
Keyword(s):  
Cytochrome C ◽  
Cell Survival ◽  
Expression Profile ◽  
Tumour Cell ◽  
Warburg Effect ◽  
Glycolytic Enzymes ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
The Warburg Effect

Introduction: GBMs are resistant to apoptosis induced by the hypoxic microenvironment and standard therapies including radiation and chemotherapy. We postulate that the Warburg effect, a preferential glycolytic phenotype of tumor cells even under aerobic conditions, plays a role in these aberrant pro-survival signals. In this study we quantitatively examined the expression profile of hypoxia-related glycolytic genes within pathologically- and MRI-defined “centre” and “periphery” of GBMs. We hypothesize that expression of hypoxia-induced glycolytic genes, particularly hexokinase 2 (HK2), favours cell survival and modulates resistance to tumour cell apoptosis by inhibiting the intrinsic mitochondrial apoptotic pathway. Methods: GBM patients underwent conventional T1-weighted contrast-enhanced MRI and MR spectroscopy studies on a 3.0T GE scanner, prior to stereotactic sampling (formalin and frozen) from regions which were T1-Gad enhancing (“centre”) and T2-positive, T1-Gad negative (“periphery”). Real-time qRT-PCR was performed to quantify regional gene expression of glycolytic genes including HK2. In vitro functional studies were performed in U87 and U373 GBM cell lines grown in normoxic (21% pO2) and hypoxic (< 1%pO2) conditions, transfected with HK2 siRNA followed by measurement of cell proliferation (BrdU), apoptosis (activated caspase 3/7, TUNEL, cytochrome c release) and viability (MTS assay). Results: There exists a differential expression profile of glycolytic enzymes between the hypoxic center and relatively normoxic periphery of GBMs. Under hypoxic conditions, there is increased expression of HK2 at the mitochondrial membrane in GBM cells. In vitro HK2 knockdown led to decreased cell survival and increased apoptosis via the intrinsic mitochondrial pathway, as seen by increased mitochondrial release of cytochrome-C. Conclusions: Increased expression of HK2 in the centre of GBMs promotes cell survival and confers resistance to apoptosis, as confirmed by in vitro studies. In vivo intracranial xenograft studies with injection of HK2-shRNA are currently being performed. HK2 and possibly other glycolytic enzymes may provide a target for enhanced therapeutic responsiveness thereby improving prognosis of patients with GBMs.

129: Semaphorin7A increases growth and metastasis of mammary tumours by promoting tumour cell survival and motility

2014 ◽  
Vol 50 ◽  
pp. S28-S29
Author(s):  
R. Garcia-Areas ◽  
S. Libreros ◽  
S. Amat ◽  
C. Castro-Silva ◽  
P. Robinson ◽  
...  
Keyword(s):  
Cell Survival ◽  
Tumour Cell ◽  
Mammary Tumours

scholarly journals Tumour cell survival signalling by the ERK1/2 pathway

2008 ◽  
Vol 16 (3) ◽  
pp. 368-377 ◽  
Author(s):  
K Balmanno ◽  
S J Cook
Keyword(s):  
Cell Survival ◽  
Tumour Cell

scholarly journals Increased expression of LAT1 in basal cell carcinoma – implications for tumour cell survival

2021 ◽  
Author(s):  
S. Prosén ◽  
E. Tina ◽  
A.H. Sneckenborg ◽  
C. Loinder ◽  
O. Seifert ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Survival ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Tumour Cell

Abstract 20500: Trx1 Promotes Trans-Nitrosylation of Cellular Proteins to Stimulate Autophagy and Cell Survival

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Narayani Nagarajan ◽  
Sebastiano Sciarretta ◽  
Junichi Sadoshima
Keyword(s):  
Cell Survival ◽  
Critical Role ◽  
Protein S ◽  
Cellular Protein ◽  
Cellular Proteins ◽  
Redox Activity ◽  
Energy Stress ◽  
Biotin Switch

Thioredoxin-1 (Trx1) is cardioprotective during oxidative stress, mainly through its antioxidant activity. Trx1 is also S-nitrosylated and, in turn, trans-nitrosylates other proteins. However, the role of Trx1-dependent S-nitrosylation in cardiomyocytes (CMs) is unknown. Here, we investigated the role of Trx1-mediated protein S-nitrosylation in the regulation of CM survival during stress in vitro. Using biotin-switch assays, we found that wild-type Trx1 (Trx1WT) is S-nitrosylated at baseline, but the extent of S-nitrosylation was attenuated in Trx1C73S, suggesting that Trx1 is S-nitrosylated at Cys73. Trx1WT and Trx1C73S do not differ in their redox activity, as determined by Amplex Red assays. Cellular protein S-nitrosylation levels were increased after 4 hours of glucose deprivation (GD), an energy stress condition (1.64±0.27 fold, p<0.05), as determined by biotin switch assays. Overexpression of Trx1WT increased (3.94-fold), whereas knockdown of Trx1 (0.66±0.01 fold, p<0.01) or overexpression of Trx1C73S (0.77±0.02 fold, p<0.01) decreased, total protein S-nitrosylation in response to GD. These results suggest that Trx1C73 regulates protein S-nitrosylation in CMs during GD. Overexpression of Trx1 increased CM survival after 24 hours of GD (1.42±0.08 fold vs LacZ, p<0.05), as evaluated with propidium iodide assays. Conversely, shTrx1 (2.13±0.05 fold vs control, p<0.01) or Trx1C73S (1.73±0.034 fold vs LacZ, p<0.01) increased cell death during GD. Either knockdown of Trx1 (LC3-II/Tubulin: 0.55 fold vs control) or overexpression of Trx1C73S (vs LacZ: LC3-II/Tubulin, 0.60 fold; autophagosomes, 0.83±0.16-fold, p<0.005; autolysosomes, 0.62±0.13-fold, p<0.005) significantly decreased autophagy during GD. Mechanistically, Trx1 co-immunoprecipitates with Atg7, an E1-like protein which plays a critical role in mediating autophagy. Using mass spectroscopy analyses, we found that SNO-Trx1 can trans-nitrosylate Atg7 in vitro. These results suggest that Trx1 trans-nitrosylates Atg7 during GD. Taken all together, our results indicate that Trx1 promotes trans-nitrosylation of cellular proteins, including Atg7, and autophagy, thereby promoting cell survival during energy stress in CMs.

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