scholarly journals TMX1 determines cancer cell metabolism as a thiol-based modulator of ER–mitochondria Ca2+ flux

2016 ◽  
Vol 214 (4) ◽  
pp. 433-444 ◽  
Author(s):  
Arun Raturi ◽  
Tomás Gutiérrez ◽  
Carolina Ortiz-Sandoval ◽  
Araya Ruangkittisakul ◽  
Maria Sol Herrera-Cruz ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cancer Cells ◽  
Tumor Tissue ◽  
Cell Metabolism ◽  
Chemotherapy Resistance ◽  
Regulatory Proteins ◽  
Tumor Mass ◽  
Atp Production ◽  
Cancer Cell Metabolism ◽  
Low Levels

The flux of Ca2+ from the endoplasmic reticulum (ER) to mitochondria regulates mitochondria metabolism. Within tumor tissue, mitochondria metabolism is frequently repressed, leading to chemotherapy resistance and increased growth of the tumor mass. Therefore, altered ER–mitochondria Ca2+ flux could be a cancer hallmark, but only a few regulatory proteins of this mechanism are currently known. One candidate is the redox-sensitive oxidoreductase TMX1 that is enriched on the mitochondria-associated membrane (MAM), the site of ER–mitochondria Ca2+ flux. Our findings demonstrate that cancer cells with low TMX1 exhibit increased ER Ca2+, accelerated cytosolic Ca2+ clearance, and reduced Ca2+ transfer to mitochondria. Thus, low levels of TMX1 reduce ER–mitochondria contacts, shift bioenergetics away from mitochondria, and accelerate tumor growth. For its role in intracellular ER–mitochondria Ca2+ flux, TMX1 requires its thioredoxin motif and palmitoylation to target to the MAM. As a thiol-based tumor suppressor, TMX1 increases mitochondrial ATP production and apoptosis progression.

scholarly journals Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

2014 ◽  
Vol 369 (1638) ◽  
pp. 20130098 ◽  
Author(s):  
Anne Poder Andersen ◽  
José M. A. Moreira ◽  
Stine Falsig Pedersen
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Ph Regulation ◽  
Cell Metabolism ◽  
Chemotherapy Resistance ◽  
Tumour Microenvironment ◽  
Ph Profile ◽  
Membrane Transport Proteins ◽  
Cancer Cell Metabolism

Major changes in intra- and extracellular pH homoeostasis are shared features of most solid tumours. These changes stem in large part from the metabolic shift of most cancer cells towards glycolytic metabolism and other processes associated with net acid production. In combination with oncogenic signalling and impact from factors in the tumour microenvironment, this upregulates acid-extruding plasma membrane transport proteins which maintain intracellular pH normal or even more alkaline compared with that of normal cells, while in turn acidifying the external microenvironment. Mounting evidence strongly indicates that this contributes significantly to cancer development by favouring e.g. cancer cell migration, invasion and chemotherapy resistance. Finally, while still under-explored, it seems likely that non-cancer cells in the tumour microenvironment also exhibit altered pH regulation and that this may contribute to their malignant properties. Thus, the physical tumour microenvironment and the cancer and stromal cells within it undergo important reciprocal interactions which modulate the tumour pH profile, in turn severely impacting on the course of cancer progression. Here, we summarize recent knowledge of tumour metabolism and the tumour microenvironment, placing it in the context of tumour pH regulation, and discuss how interfering with these properties may be exploited clinically.

scholarly journals Extracellular Citrate Fuels Cancer Cell Metabolism and Growth

2020 ◽  
Vol 8 ◽  
Author(s):  
Sebastian Haferkamp ◽  
Konstantin Drexler ◽  
Marianne Federlin ◽  
Hans J. Schlitt ◽  
Mark Berneburg ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Metabolism ◽  
Mitochondrial Activity ◽  
Cancer Cell Proliferation ◽  
Atp Production ◽  
Proliferation And Metastasis ◽  
Cancer Cell Metabolism ◽  
The Impact ◽  
Cell Proliferation And Metastasis

Cancer cells need excess energy and essential nutrients/metabolites not only to divide and proliferate but also to migrate and invade distant organs for metastasis. Fatty acid and cholesterol synthesis, considered a hallmark of cancer for anabolism and membrane biogenesis, requires citrate. We review here potential pathways in which citrate is synthesized and/or supplied to cancer cells and the impact of extracellular citrate on cancer cell metabolism and growth. Cancer cells employ different mechanisms to support mitochondrial activity and citrate synthesis when some of the necessary substrates are missing in the extracellular space. We also discuss the different transport mechanisms available for the entry of extracellular citrate into cancer cells and how citrate as a master metabolite enhances ATP production and fuels anabolic pathways. The available literature suggests that cancer cells show an increased metabolic flexibility with which they tackle changing environmental conditions, a phenomenon crucial for cancer cell proliferation and metastasis.

Apoptosis triggered by isoquercitrin in bladder cancer cells by activating the AMPK-activated protein kinase pathway

2017 ◽  
Vol 8 (10) ◽  
pp. 3707-3722 ◽  
Author(s):  
Ping Wu ◽  
Siyuan Liu ◽  
Jianyu Su ◽  
Jianping Chen ◽  
Lin Li ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Metabolism ◽  
Bladder Cancer Cell ◽  
Bladder Cancer Cells ◽  
Immunoblotting Assay ◽  
Cancer Cell Metabolism ◽  
Kinase Pathway

Our findings provide comprehensive evidence that isoquercitrin (ISO) influenced T24 bladder cancer cell metabolism by activating the AMPK pathway as identified by combination with metabolomics and immunoblotting assay.

scholarly journals The Neglected Liaison: Targeting Cancer Cell Metabolic Reprogramming Modifies the Composition of Non-Malignant Populations of the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5447
Author(s):  
Maria Iorio ◽  
Nikkitha Umesh Ganesh ◽  
Monica De Luise ◽  
Anna Maria Porcelli ◽  
Giuseppe Gasparre ◽  
...  
Keyword(s):  
Complex System ◽  
Clinical Trials ◽  
Cancer Cell ◽  
Immune Cells ◽  
Cell Metabolism ◽  
Metabolic Reprogramming ◽  
Preclinical Studies ◽  
Tumor Mass ◽  
Cancer Cell Metabolism ◽  
Target Cancer

Metabolic reprogramming is a well-known hallmark of cancer, whereby the development of drugs that target cancer cell metabolism is gaining momentum. However, when establishing preclinical studies and clinical trials, it is often neglected that a tumor mass is a complex system in which cancer cells coexist and interact with several types of microenvironment populations, including endothelial cells, fibroblasts and immune cells. We are just starting to understand how such populations are affected by the metabolic changes occurring in a transformed cell and little is known

scholarly journals Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes

2017 ◽  
Vol 8 (1) ◽  
pp. 631-640 ◽  
Author(s):  
Jian-Jun Cao ◽  
Cai-Ping Tan ◽  
Mu-He Chen ◽  
Na Wu ◽  
De-Yang Yao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Rational Design ◽  
Cell Metabolism ◽  
Mitochondrial Metabolism ◽  
Cancer Cell Metabolism

We report a rational design and mechanism studies of mitochondria-immobilized iridium(iii) complexes that can kill cancer cells by targeting mitochondrial metabolism.

Targeting Cancer Cell Metabolism: The Combination of Metformin and 2-Deoxyglucose Induces p53-Dependent Apoptosis in Prostate Cancer Cells

2010 ◽  
Vol 70 (6) ◽  
pp. 2465-2475 ◽  
Author(s):  
Issam Ben Sahra ◽  
Kathiane Laurent ◽  
Sandy Giuliano ◽  
Frédéric Larbret ◽  
Gilles Ponzio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Metabolism ◽  
Prostate Cancer Cells ◽  
Cancer Cell Metabolism

scholarly journals Metabolic Heterogeneity of Cancer Cells: An Interplay between Reprogrammed and Oxidative Metabolism and Roles of HIF-1, GLUTs and AMPK

2020 ◽  
Author(s):  
Nurbubu T. Moldogazieva ◽  
Innokenty M. Mokhosoev ◽  
Alexander A. Terentiev
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Oxidative Metabolism ◽  
Cell Metabolism ◽  
Hypoxia Inducible Factor ◽  
Metabolic Plasticity ◽  
Anti Cancer ◽  
Cancer Cell Metabolism ◽  
Metabolic Heterogeneity ◽  
Amp Activated Protein Kinase

It has been long recognized that under hypoxia conditions cancer cells reprogram their metabolism through shift from oxidative phosphorylation (OXPHOS) to glycolysis to meet elevated requirements in energy and nutrients for proliferation, migration and survival. However, data accumulated over the last years increasingly evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism even in the same tumor. The phenomenon denoted as cancer cell metabolic plasticity or hybrid metabolism depends on a tumor micro-environment, which is highly heterogeneous and influenced by intensity of vasculature and blood flow, oxygen concentration, nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, reactive oxygen species (ROS), etc. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, GLUTs, and AMPK and other regulatory proteins including oncogenes such as c-Myc, p53 and KRAS, growth factor-initiated PKB/Akt, PI3K and mTOR signaling pathways and tumor suppressors such as LKB1 and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discovery novel anti-cancer drugs.

Metabolic and amino acid alterations of the tumor microenvironment

2020 ◽  
Vol 27 ◽  
Author(s):  
Petr Stepka ◽  
Vit Vsiansky ◽  
Martina Raudenska ◽  
Jaromir Gumulec ◽  
Vojtech Adam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Amino Acids ◽  
Amino Acid ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Warburg Effect ◽  
Cell Metabolism ◽  
Metastatic Potential ◽  
Cancer Cell Metabolism

: Metabolic changes driven by the hostile tumor microenvironment surrounding cancer cells and effect of these changes on tumorigenesis and metastatic potential have been known for a long time. The usual point of interest is glucose and changes in its utilization by cancer cells, mainly in the form of the Warburg effect. However, amino acids, both intra- and extracellular, also represent an important aspect of tumour microenvironment, which can have a significant effect on cancer cell metabolism and overall development of the tumor. Namely alterations in metabolism of amino acids glutamine, sarcosine, aspartate, methionine and cysteine have been previously connected to the tumor progression and aggressivity of prostate cancer. The aim of this review is to pinpoint current gaps in our knowledge of the role of amino acids as a part of the tumor microenvironment and to show effect of various amino acids on cancer cell metabolism and metastatic potential. This review shows limitations and exceptions from the traditionally accepted model of Warburg effect in some cancer tissues, with the emphasis on prostate cancer, because the traditional definition of Warburg effect as a metabolic switch to aerobic glycolysis does not always apply. Prostatic tissue both in healthy and transformed state significantly differs in many metabolic aspects, including the metabolisms of glucose and amino acids, from metabolism of other tissues. Findings from different tissues are therefore not always interchangeable and have to be taken into account during experimentation modifying the environment of tumor tissue by amino acid supplementation or depletion, which could potentially serve as a new therapeutic approach.

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.

Cancer Cell Metabolism Featuring Nrf2

2020 ◽  
Vol 17 (3) ◽  
pp. 263-271 ◽  
Author(s):  
Payal Chatterjee ◽  
Mukesh Yadav ◽  
Namrata Chauhan ◽  
Ying Huang ◽  
Yun Luo
Keyword(s):  
Cancer Cells ◽  
Cell Metabolism ◽  
Cellular Metabolism ◽  
Energy Requirements ◽  
Genetic Mutations ◽  
Cellular Protection ◽  
Key Factor ◽  
Cancer Cell Metabolism ◽  
Cancerous Cells

Although the major role of Nrf2 has long been established as a transcription factor for providing cellular protection against oxidative stress, multiple pieces of research and reviews now claim exactly the opposite. The dilemma - “to activate or inhibit” the protein requires an immediate answer, which evidently links cellular metabolism to the causes and purpose of cancer. Profusely growing cancerous cells have prolific energy requirements, which can only be fulfilled by modulating cellular metabolism. This review highlights the cause and effect of Nrf2 modulation in cancer that in turn channelize cellular metabolism, thereby fulfilling the energy requirements of cancer cells. The present work also highlights the purpose of genetic mutations in Nrf2, in relation to cellular metabolism in cancer cells, thus pointing out a newer approach where parallel mutations may be the key factor to decide whether to activate or inhibit Nrf2.

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