scholarly journals GRP78 enhances the glutamine metabolism to support cell survival from glucose deficiency by modulating the β-catenin signaling

Oncotarget ◽  
2014 ◽  
Vol 5 (14) ◽  
pp. 5369-5380 ◽  
Author(s):  
Zongwei Li ◽  
Yingying Wang ◽  
Haili Wu ◽  
Lichao Zhang ◽  
Peng Yang ◽  
...  
2014 ◽  
Vol 35 (6) ◽  
pp. 1682-1691 ◽  
Author(s):  
Du Cheng ◽  
Leiliang Zhang ◽  
Guangbo Yang ◽  
Lei Zhao ◽  
Feng Peng ◽  
...  

2002 ◽  
Vol 30 (4) ◽  
pp. 360-365 ◽  
Author(s):  
S. C. Masters ◽  
R. R. Subramanian ◽  
A. Truong ◽  
H. Yang ◽  
K. Fujii ◽  
...  

The 14-3-3 proteins are a family of phosphoserine/phosphothreonine-binding molecules that control the function of a wide array of cellular proteins. We suggest that one function of 14-3-3 is to support cell survival. 14-3-3 proteins promote survival in part by antagonizing the activity of associated proapoptotic proteins, including Bad and apoptosis signal-regulating kinase 1 (ASK1). Indeed, expression of 14-3-3 inhibitor peptides in cells is sufficient to induce apoptosis. Interestingly, these 14-3-3 antagonist peptides can sensitize cells for effective killing by anticancer agents such as cisplatin. Thus, 14-3-3 may be part of the cellular machinery that maintains cell survival, and targeting 14-3-3-ligand interactions may be a useful strategy to enhance the efficacy of conventional anticancer agents.


2021 ◽  
Author(s):  
Madeline P Sheeley ◽  
Violet A Keisel ◽  
Nadia M. Atallah ◽  
Shawn S. Donkin ◽  
Stephen D. Hursting ◽  
...  

Abstract Background: Throughout metastatic progression, cancer cells acquire anchorage independence, or the ability to survive detached from the extracellular matrix (ECM). While untransformed epithelial cells reduce energy metabolism when detached, cancer cells display metabolic flexibility to continue important metabolic processes. Glucose and glutamine are predominant nutrients utilized for energy as well as other purposes, and their metabolism is regulated by cancer cells.Methods: The purpose of the current studies was to determine the effects of detachment on glucose and glutamine metabolism in human breast epithelial MCF10A cells transfected with the Harvey-ras oncogene (MCF10A-ras), a model of early-stage cancer. Detachment was simulated with poly-HEMA coated plates, and intracellular metabolic flux was determined using stably labeled 13C5-glutamine and 13C6-glucose tracers.Results: Results show reduced glutamine flux in detached cells as determined by reduced accumulation of label in glutamate (21%), malate (30%), and aspartate (23%) from 13C5-glutamine. Detachment also reduced flux of 13C6-glucose to pyruvate and lactate pools by 51% and 29%, respectively. Similarly, detachment reduced total intracellular pool sizes of pyruvate (51%), lactate (49%), α-ketoglutarate (43%), fumarate (32%), malate (19%), alanine (35%), serine (35%), and glutamate (28%) compared to attached cells, but citrate and aspartate pool sizes were unchanged. Compared to attached cells, detachment increased pyruvate carboxylase (PC) mRNA abundance and protein expression by 131% and 190%, respectively. In detachment, PC activity, determined by 13C6-glucose derived M + 3 isotopomers, was shown to preferentially replenish malate and aspartate, but not citrate pools. In addition, doxycycline-inducible shRNA depletion of PC significantly decreased, while doxycycline-inducible PC overexpression significantly increased, detached cell viability. Further, a switch from glutamine to PC activity for anaplerosis was demonstrated, as supplementation with the cell permeable analog of the tricarboxylic acid cycle intermediate, α-ketoglutarate, a downstream metabolite of glutamine, decreased PC mRNA abundance in detached cells.Conclusion: Collectively, these results suggest that detached breast cancer cells increase PC activity in response to decreased glutamine-derived anaplerosis to promote cell survival.


2020 ◽  
Vol 21 (2) ◽  
Author(s):  
Christy Mikhael ◽  
Shannon Holliday ◽  
Guanghong Han

Extracellular vesicles (EVs) are 30-150 nm in diameter and are released by cells into the extracellular environment. They facilitate intercellular communication and may be involved in cell survival. Although serum-dependent cells are not obviously affected by depletion of EVs from the serum, we previously reported that cells in serum that contain EVs were more resistant to the drugs, enoxacin and bis-enoxacin, compared to cells in serum without EVs. This change in resistance led us to examine whether EVs are sufficient to maintain serum dependent cells in vitro. Here, we tested the effect of EVs on the survival RAW 264.7 cells and on 4T1 murine breast cancer cells. EVs were isolated by differential centrifugation. EVs were counted over various time periods. Cells were grown in alpha or Dulbecco’s minimal essential media supplemented with FBS, EVs from various sources, or with no supplements. Cell growth was determined by cell counts. In media without supplementation, the RAW 264.7 cells and 4T1 cells died by three days. Media supplemented with EVs from FBS allowed the cells to survive in the absence of FBS for one week or more.  Being able to perform experiments on cells supported by EVs will simplify the interpretation of experiments. Efforts are underway to determine their mechanism by which EVs support cell survival.


Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1231-1238 ◽  
Author(s):  
B. Kerber ◽  
I. Monge ◽  
M. Mueller ◽  
P.J. Mitchell ◽  
S.M. Cohen

Flies mutant for the Drosophila homologue of the mammalian transcription factor AP-2 show a severe reduction in leg length and fail to develop joint structures. Presumptive joint cells express dAP-2 in response to Notch signaling. dAP-2 is required for joint cell differentiation and can induce formation of supernumerary joints when misexpressed. Although dAP-2 is expressed only in presumptive joint cells, its activity is required to support cell survival in the entire leg segment. Taken together, our data indicate that dAP-2 is an important mediator of Notch activity in leg development.


Author(s):  
D.E. Philpott ◽  
W. Sapp ◽  
C. Williams ◽  
J. Stevenson ◽  
S. Black ◽  
...  

Spermatogonial stem-cell survival after irradiation injury has been studied in rodents by histological counts of surviving cells. Many studies, including previous work from our laboratory, show that the spermatogonial population demonstrates a heterogeneous response to irradiation. The spermatogonia increase in radio-sensitivity as differentiation proceeds through the sequence As - Apr - A1 - A2 - A3 - A4 - In - B. The stem (As) cell is the most resistant and the B cell is the most sensitive. The purpose of this work is to investigate the response of spermatogonial cell to low doses (less than 10 0 rads) of helium particle irradiation.


2008 ◽  
Vol 18 (3) ◽  
pp. 119-125
Author(s):  
Sarah Klemuk

Abstract Collaborative studies at the University of Iowa and the National Center for Voice and Speech aim to help the voices of teachers. Investigators study how cells and tissues respond to vibration doses simulating typical vocalization patterns of teachers. A commercially manufactured instrument is uniquely modified to support cell and tissue growth, to subject tissues to vocalization-like forces, and to measure viscoelastic properties of tissues. Through this basic science approach, steps toward safety limits for vocalization and habilitating rest periods for professional voice users will be achieved.


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