scholarly journals Acid Gradient Across Plasma Membrane can Drive Phosphate‐Bond Synthesis in Cancer Cells: Acidic Tumor Milieu can Act as a Potential Energy Source

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Gautam Dhar ◽  
Suvajit Sen ◽  
Gautam Chaudhuri
2021 ◽  
pp. 101012
Author(s):  
Anne Sofie Busk Heitmann ◽  
Ali Asghar Hakami Zanjani ◽  
Martin Berg Klenow ◽  
Anna Mularski ◽  
Stine Lauritzen Sønder ◽  
...  

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii225-ii226
Author(s):  
Vahan Martirosian ◽  
Krutika Deshpande ◽  
Hao Zhou ◽  
Keyue Shen ◽  
Vazgen Stepanosyan ◽  
...  

Abstract Medulloblastoma (MB) is a malignant pediatric brain tumor. Studies have shown heterogeneous cells amongst the tumor bulk which mirror normal neural cells in various neurodevelopmental stages. To discern exploited mechanisms promoting MB leptomeningeal disease, we drew conclusions from developmental neurobiology. In normal differentiation, the metabolic phenotype in proliferating neural progenitor cells evolves from a glycolysis-dependent to an oxidative phosphorylation-reliant energetic profile in quiescent differentiated neurons. Cancer cells mirror this evolution, which also grants them the capability to utilize alternative nutrients in the microenvironment as an energy source. Considering metastatic cells are typically in a dormant state and primarily utilize oxidative phosphorylation, we hypothesized metastatic MB cells emulate a quiescent neuron-like cellular profile to survive in the cerebrospinal fluid and form leptomeningeal metastases. To examine this, we query the expression of GABA catabolic enzyme GABA transaminase (ABAT) in MB. GABA is found in the cerebellar and leptomeningeal microenvironments, and is utilized by metastatic cancer cells in the CNS as an energy source. We correlate an increase in ABAT expression with neurodevelopment and show heterogeneous expression of this protein in primary MB tumors. MB cells with increased expression of ABAT were slower-dividing, expressed a genetic and metabolic phenotype reminiscent of quiescent neuron-like cells, and had increased capability to metabolize GABA. Conversely, lower expression of ABAT was associated with an increased proliferation rate and correlated with a progenitor-like cellular profile. Transplantation of MB cells into the leptomeningeal compartment decreased proliferative capacity and enhanced ABAT expression. Xenograft models showed MB cells with ABAT knockdown had increased growth in the cerebellar microenvironment. Conversely, MB cells with ABAT overexpression transplanted into the cerebrospinal fluid formed leptomeningeal metastases whereas ABAT knockdown cells could not. These results suggest ABAT expression in MB cells can be modulated by the tumor microenvironment and is required to form leptomeningeal metastases.


2021 ◽  
Vol 22 (15) ◽  
pp. 8165
Author(s):  
Amanda Chantziou ◽  
Kostas Theodorakis ◽  
Hara Polioudaki ◽  
Eelco de Bree ◽  
Marilena Kampa ◽  
...  

In breast cancer, expression of Cluster of Differentiation 24 (CD24), a small GPI-anchored glycoprotein at the cell periphery, is associated with metastasis and immune escape, while its absence is associated with tumor-initiating capacity. Since the mechanism of CD24 sorting is unknown, we investigated the role of glycosylation in the subcellular localization of CD24. Expression and localization of wild type N36- and/or N52-mutated CD24 were analyzed using immunofluorescence in luminal (MCF-7) and basal B (MDA-MB-231 and Hs578T) breast cancer cells lines, as well as HEK293T cells. Endogenous and exogenously expressed wild type and mutated CD24 were found localized at the plasma membrane and the cytoplasm, but not the nucleoplasm. The cell lines showed different kinetics for the sorting of CD24 through the secretory/endocytic pathway. N-glycosylation, especially at N52, and its processing in the Golgi were critical for the sorting and expression of CD24 at the plasma membrane of HEK293T and basal B type cells, but not of MCF-7 cells. In conclusion, our study highlights the contribution of N-glycosylation for the subcellular localization of CD24. Aberrant N-glycosylation at N52 of CD24 could account for the lack of CD24 expression at the cell surface of basal B breast cancer cells.


2020 ◽  
Vol 477 (15) ◽  
pp. 2893-2919
Author(s):  
Walaa E. Kattan ◽  
John F. Hancock

The three human RAS proteins are mutated and constitutively activated in ∼20% of cancers leading to cell growth and proliferation. For the past three decades, many attempts have been made to inhibit these proteins with little success. Recently; however, multiple methods have emerged to inhibit KRAS, the most prevalently mutated isoform. These methods and the underlying biology will be discussed in this review with a special focus on KRAS-plasma membrane interactions.


2003 ◽  
Vol 1 (5) ◽  
pp. S290
Author(s):  
A.A. Gutiérrez ◽  
D. González-Espinosa ◽  
J. Hernández ◽  
A. Guerrero-Hernández ◽  
F. Martinez ◽  
...  

1997 ◽  
Vol 43 (7) ◽  
pp. 683-687 ◽  
Author(s):  
Alexandra Veiga ◽  
Ana Ferreira Pinto ◽  
Maria C. Loureiro-Dias

Rhodotorula ferulica, a yeast able to utilize phenolic compounds, was chosen for evaluating the effects of tributyltin oxide (TBTO) on this utilization. TBTO reduced respiratory capacity when vanillic or benzoic acid was the energy source. The ATP level of the cells was severely affected by 2 μM TBTO. The mitochondrial ATPase was strongly inhibited by 0.5 μM TBTO, whereas the activity of the plasma membrane ATPase was not affected by concentrations of TBTO up to 30 μM. Our data support the hypothesis that the target for TBTO action is the mitochondrial ATPase, resulting in a severe disturbance of the yeast utilization of aromatic compounds.Key words: TBTO, tributyltin, yeast, Rhodotorula ferulica, respiration, ATPase.


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