scholarly journals USP28 promotes aerobic glycolysis of colorectal cancer by increasing stability of FOXC1

2021 ◽  
Author(s):  
Zhaohui Liu ◽  
Min Chen ◽  
Xiaoping Xu ◽  
Lei Zhang ◽  
Yuan Pan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Viability ◽  
Cancer Cell ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Over Expression ◽  
Cancer Cell Metabolism ◽  
Cancer Tissues

Aerobic glycolysis is essential for cancer cell metabolism and growth. Deubiquitinase, USP28 (ubiquitin specific peptidase 28), could maintain stability of proteins involved in tumor progression. This study was performed to investigate the role of USP28 in aerobic glycolysis of colorectal cancer. Our data showed that USP28 mRNA and protein expressions were enhanced in colorectal cancer tissues and cells. Functional assays demonstrated that overexpression of USP28 promoted cell proliferation and aerobic glycolysis of colorectal cancer, while USP28 inhibition could reverse these effects. Protein expression of Forkhead Box C1 (FOXC1) was increased by USP28 over-expression, whereas knockdown of USP28 aggravated cycloheximide (CHX; protein synthesis inhibitor) stimulated decrease of FOXC1. Moreover, proteasome inhibitor, MG132, could rescue USP28 silence-induced degradation of FOXC1. Overexpression of FOXC1 counteracted the suppressive effects of USP28 interference on colorectal cancer cell viability and aerobic glycolysis. In conclusion, USP28 enhanced cell viability and aerobic glycolysis of colorectal cancer by stabilizing FOXC1, suggesting that USP28-FOXC1 might be a novel therapeutic avenue for colorectal cancer.

scholarly journals miR-142-3p Modulates Cell Invasion and Migration via PKM2-Mediated Aerobic Glycolysis in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
JunYu Ren ◽  
Wenliang Li ◽  
Guoqing Pan ◽  
Fengchang Huang ◽  
Jun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pyruvate Kinase ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Aerobic Glycolysis ◽  
Cancer Cell Invasion ◽  
Human Colorectal Cancer ◽  
Invasion And Migration ◽  
And Migration ◽  
Cancer Tissues

Decreased expression of miR-142-3p was observed in human cancers. However, the function and mechanism of miR-142-3p in human colorectal cancer remain obscure. The expressions of miR-142-3p in human colorectal cancer tissues and cell lines were measured by RT-qPCR. The effects of miR-142-3p on cell invasion and migration were detected by transwell assays. The efficiency of aerobic glycolysis was determined by glucose consumption and lactate production. Dual-luciferase reporter assays were performed to confirm the correlation between miR-142-3p and pyruvate kinase isozyme M2 (PKM2). The level of PKM2 was assessed by western blotting. Our results showed that the expression of miR-142-3p was decreased both in human colorectal cancer tissues and in cells. Overexpression of miR-142-3p in cell line attenuated colorectal cancer cell invasion and migration. About the underlying mechanism, we found that miR-142-3p modulated aerobic glycolysis via targeting pyruvate kinase M2 (PKM2). In addition, we demonstrated PKM2 and PKM2-mediated aerobic glycolysis contributes to miR-142-3p-mediated colorectal cancer cell invasion and migration. Hence, these data suggested that miR-142-3p was a potential therapeutic target for the treatment of human colorectal cancer.

Pieces of the complex puzzle of cancer cell energy metabolism: an overview of energy metabolism and alternatives for targeted cancer therapy

2020 ◽  
Vol 27 ◽  
Author(s):  
Zeinab Ghasemishahrestani ◽  
Larissa Maura Melo Mattos ◽  
Tatiana Martins Tilli ◽  
André Souza dos Santos ◽  
Marcos Dias Pereira
Keyword(s):  
Energy Metabolism ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Warburg Effect ◽  
Cell Biology ◽  
Aerobic Glycolysis ◽  
Target Therapy ◽  
Cell Metabolism ◽  
Cancer Cell Metabolism

Over the past decades, several advances in cancer cell biology have led to relevant details about a phenomenon called "Warburg effect". Currently, it has been accepted that Warburg effect is not anymore compatible with all cancer cells, and thus the process of aerobic glycolysis is now challenged by the knowledge of a large number of cells presenting mitochondrial function. The energy metabolism of cancer cells is focused in the bioenergetic and biosynthetic pathways to meet the requirements of rapid proliferation. Changes in the metabolism of carbohydrate, amino acids and lipids have already been reported in cancer cells and might play relevant roles for cancer progression. To the best of our knowledge, mostly of these changes are established, mainly due to genetic reprogramming that leads to the transformation of a healthy into a cancerous cell. Indeed, several enzymes of high relevance for the energy are targets of oncogenes (ex. PI3K, HIF1 and Myc) and tumor suppressor proteins (ex. p53). As a consequence of the extensive study on cancer cell metabolism, some new therapeutic strategies have appeared that aim to interrupt the aberrant metabolism, as well as the influence of genetic reprogramming in cancer cells. In this perspective, we briefly review the cancer cell metabolism (carbohydrate, amino acid and lipid), and also describe oncogenes and tumor suppressors that affect cancer cell metabolism. We also discuss some potential candidates for target therapy to disrupt the main driven-force for cancer cell metabolism and proliferation.

scholarly journals Targeting colorectal cancer cell metabolism through development of cisplatin and metformin nano-cubosomes

BMC Cancer ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Mona M. Saber ◽  
Abdulaziz M. Al-mahallawi ◽  
Noha N. Nassar ◽  
Björn Stork ◽  
Samia A. Shouman
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
Cell Metabolism ◽  
Colorectal Cancer Cell ◽  
Cancer Cell Metabolism

scholarly journals Dynamics of resource allocation in Biological Systems II: On cancer cell metabolism

2016 ◽  
Author(s):  
Imadol V Jeff-Eke
Keyword(s):  
Resource Allocation ◽  
Cancer Cell ◽  
Normal Cell ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Biological Systems ◽  
High Resource ◽  
Resource Requirements ◽  
Initial Work ◽  
Cancer Cell Metabolism

Here we shall apply the approach presented in the paper Dynamics of resource allocation in biological systems in considering resource allocation in cancer cell metabolism, specifically, aerobic glycolysis (Warburg effect). Aerobic glycolysis, the metabolic phenomenon of cells utilizing glucose fermentation to lactate even under conditions of ample oxygen availability. We shall consider resource reallocations between processes of two hypothetical cells: a cancer cell and a normal cell. Specifically, we consider reallocation of resources between cancer-related processes of a cancer cell, normal processes of same cancer cell, and processes of a normal cell in attempts to satisfy the high resource requirements for cancer-related processes. In doing this, we draw inferences from the initial work and state hypotheses as pertains to cancer cell metabolism. From this hypotheses, we shall attempt explanation of Aerobic glycolysis. We end by considering genomic instability as a derivation of cancer cell metabolism.

scholarly journals Dynamics of resource allocation in Biological Systems II: On cancer cell metabolism

2016 ◽  
Author(s):  
Imadol V Jeff-Eke
Keyword(s):  
Resource Allocation ◽  
Cancer Cell ◽  
Normal Cell ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Biological Systems ◽  
High Resource ◽  
Resource Requirements ◽  
Initial Work ◽  
Cancer Cell Metabolism

Here we shall apply the approach presented in the paper Dynamics of resource allocation in biological systems in considering resource allocation in cancer cell metabolism, specifically, aerobic glycolysis (Warburg effect). Aerobic glycolysis, the metabolic phenomenon of cells utilizing glucose fermentation to lactate even under conditions of ample oxygen availability. We shall consider resource reallocations between processes of two hypothetical cells: a cancer cell and a normal cell. Specifically, we consider reallocation of resources between cancer-related processes of a cancer cell, normal processes of same cancer cell, and processes of a normal cell in attempts to satisfy the high resource requirements for cancer-related processes. In doing this, we draw inferences from the initial work and state hypotheses as pertains to cancer cell metabolism. From this hypotheses, we shall attempt explanation of Aerobic glycolysis. We end by considering genomic instability as a derivation of cancer cell metabolism.

Treatment of breast, ovarian and lung cancer cells by inducing apoptosis with a deep eutectic solvent prepared from 2-deoxy-D-glucose and metformin: Cancer cell metabolism as a drug target.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15599-e15599
Author(s):  
Sauli Vuoti ◽  
Jaakko Eemil ◽  
Kumar Narasimha ◽  
Kai Reinikainen
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Deep Eutectic Solvent ◽  
Migration And Invasion ◽  
Solvent Mixtures ◽  
Human Beings ◽  
Cancer Cell Metabolism

e15599 Background: Targeting cancer cell metabolism has gained attention as a future strategy to fight cancer. A characteristic of tumor cells is the elevated aerobic glycolysis for energy production. It has been shown that 2-deoxy-D-glucose (2DG) inhibits glycolysis and induces apoptotic cell death in different tumor types. The anti-diabetic drug metformin has been used in combination to enhance the inhibitory effect. So far, the attempts to combine both compounds in a clinical setting have been limited by the requirement of concentrations higher than those accessible in blood plasma of human beings. Deep eutectic solvents (DES) are solvent mixtures prepared from hydrogen bond donors and acceptors, wherein pharmaceutically active compounds can also be one of the components. Besides having unique physicochemical properties, DESs have been reported to demonstrate or enhance anticancer properties. Methods: We developed a DES mixture from 2DG and MET using a method based in mechanical grinding. We investigated the anticancer activity of conventional and DES mixtures of MET and 2DG, and used the mixtures to inhibit the growth, migration and invasion of cancer cells, and induce cell cycle arrest in vitro. Results: MET and 2DG, alone and in combination, induced apoptosis in the H460, SKOV-3, MDA-MB-231 and HCC1806 (TNBC) cell lines. Induction of apoptosis was further quantified by measurement of the loss of mitochondrial membrane potential and cleavage of PARP. DES mixtures had the highest impact on cell viability, exceeding the effect of 2DG/MET as single agents or combinations at all clinically relevant concentrations. The DES mixture with the lowest concentration to induce apoptosis consisted of 100 µM 2DG and 200 µM MET. A conventional solution with similar concentrations showed no activity. Conclusions: We developed a DES from 2DG/MET, which significantly reduced the viability of several types of cancer cells, surpassing the effect of single components or mixtures. The DES does not necessitate the use of additional solvents and could be used to develop clinical applications for targeting cancer cell metabolism.

scholarly journals A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism, Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

2021 ◽  
Vol 22 (6) ◽  
pp. 2918
Author(s):  
Eleni Papakonstantinou ◽  
Dimitrios Vlachakis ◽  
Trias Thireou ◽  
Panayiotis G. Vlachoyiannopoulos ◽  
Elias Eliopoulos
Keyword(s):  
Cancer Cell ◽  
Structural Characteristics ◽  
Cell Metabolism ◽  
Intracellular Localization ◽  
Selective Inhibition ◽  
Monocarboxylate Transporter ◽  
Cancer Drug ◽  
Pharmacophore Modelling ◽  
Anti Cancer ◽  
Cancer Cell Metabolism

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.

scholarly journals Oncolytic Virotherapy: The Cancer Cell Side

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 939
Author(s):  
Marcelo Ehrlich ◽  
Eran Bacharach
Keyword(s):  
Viral Replication ◽  
Cancer Cell ◽  
Cell Metabolism ◽  
Tumor Development ◽  
Oncolytic Viruses ◽  
Oncogenic Signaling ◽  
Functional Connection ◽  
Immunity Genes ◽  
Cancer Cell Metabolism ◽  
Editing Process

Cell autonomous immunity genes mediate the multiple stages of anti-viral defenses, including recognition of invading pathogens, inhibition of viral replication, reprogramming of cellular metabolism, programmed-cell-death, paracrine induction of antiviral state, and activation of immunostimulatory inflammation. In tumor development and/or immunotherapy settings, selective pressure applied by the immune system results in tumor immunoediting, a reduction in the immunostimulatory potential of the cancer cell. This editing process comprises the reduced expression and/or function of cell autonomous immunity genes, allowing for immune-evasion of the tumor while concomitantly attenuating anti-viral defenses. Combined with the oncogene-enhanced anabolic nature of cancer-cell metabolism, this attenuation of antiviral defenses contributes to viral replication and to the selectivity of oncolytic viruses (OVs) towards malignant cells. Here, we review the manners by which oncogene-mediated transformation and tumor immunoediting combine to alter the intracellular milieu of tumor cells, for the benefit of OV replication. We also explore the functional connection between oncogenic signaling and epigenetic silencing, and the way by which restriction of such silencing results in immune activation. Together, the picture that emerges is one in which OVs and epigenetic modifiers are part of a growing therapeutic toolbox that employs activation of anti-tumor immunity for cancer therapy.

Sign in / Sign up

Export Citation Format

Share Document