scholarly journals Metabolic functions of macropinocytosis

2018 ◽  
Vol 374 (1765) ◽  
pp. 20180285 ◽  
Author(s):  
Wilhelm Palm
Keyword(s):  
Growth Factor ◽  
Cancer Cells ◽  
Nutrient Uptake ◽  
Mammalian Cells ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Extracellular Fluid ◽  
Metabolic Functions ◽  
Evolutionarily Conserved ◽  
Growth Factor Signalling

Macropinocytosis is an evolutionarily conserved form of endocytosis that mediates non-selective uptake of extracellular fluid and the solutes contained therein. In mammalian cells, macropinocytosis is initiated by growth factor-mediated activation of the Ras and PI3-kinase signalling pathways. In malignant cells, oncogenic activation of growth factor signalling sustains macropinocytosis cell autonomously. Recent studies of cancer metabolism, discussed here, have begun to define a role for macropinocytosis as a nutrient uptake route. Macropinocytic cancer cells ingest macromolecules in bulk and break them down in the lysosome to support metabolism and macromolecular synthesis. Thereby, macropinocytosis allows cells to tap into the copious nutrient stores of extracellular macromolecules when canonical nutrients are scarce. These findings demonstrate that macropinocytosis promotes metabolic flexibility and resilience, which enables cancer cells to survive and grow in nutrient-poor environments. Implications for physiological roles of growth factor-stimulated macropinocytosis in cell metabolism and its relationship with other nutrient uptake pathways are considered. This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.

scholarly journals The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

2021 ◽  
Vol 22 (3) ◽  
pp. 1171
Author(s):  
Dexter L. Puckett ◽  
Mohammed Alquraishi ◽  
Winyoo Chowanadisai ◽  
Ahmed Bettaieb
Keyword(s):  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Metabolic Reprogramming ◽  
Circular Rnas ◽  
Tissue Specific ◽  
Cell Progression ◽  
Non Coding Rnas ◽  
Regulatory Effects

Pyruvate kinase is a key regulator in glycolysis through the conversion of phosphoenolpyruvate (PEP) into pyruvate. Pyruvate kinase exists in various isoforms that can exhibit diverse biological functions and outcomes. The pyruvate kinase isoenzyme type M2 (PKM2) controls cell progression and survival through the regulation of key signaling pathways. In cancer cells, the dimer form of PKM2 predominates and plays an integral role in cancer metabolism. This predominance of the inactive dimeric form promotes the accumulation of phosphometabolites, allowing cancer cells to engage in high levels of synthetic processing to enhance their proliferative capacity. PKM2 has been recognized for its role in regulating gene expression and transcription factors critical for health and disease. This role enables PKM2 to exert profound regulatory effects that promote cancer cell metabolism, proliferation, and migration. In addition to its role in cancer, PKM2 regulates aspects essential to cellular homeostasis in non-cancer tissues and, in some cases, promotes tissue-specific pathways in health and diseases. In pursuit of understanding the diverse tissue-specific roles of PKM2, investigations targeting tissues such as the kidney, liver, adipose, and pancreas have been conducted. Findings from these studies enhance our understanding of PKM2 functions in various diseases beyond cancer. Therefore, there is substantial interest in PKM2 modulation as a potential therapeutic target for the treatment of multiple conditions. Indeed, a vast plethora of research has focused on identifying therapeutic strategies for targeting PKM2. Recently, targeting PKM2 through its regulatory microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) has gathered increasing interest. Thus, the goal of this review is to highlight recent advancements in PKM2 research, with a focus on PKM2 regulatory microRNAs and lncRNAs and their subsequent physiological significance.

scholarly journals Fibroblast growth factor signalling induces loss of progesterone receptor in breast cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (52) ◽  
pp. 86011-86025 ◽  
Author(s):  
Dominika Piasecka ◽  
Kamila Kitowska ◽  
Dominika Czaplinska ◽  
Kamil Mieczkowski ◽  
Magdalena Mieszkowska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Progesterone Receptor ◽  
Cancer Cells ◽  
Fibroblast Growth Factor ◽  
Breast Cancer Cells ◽  
Fibroblast Growth ◽  
Growth Factor Signalling

scholarly journals The Role of Sodium Hydrogen Exchanger 1 in Dysregulation of Proton Dynamics and Reprogramming of Cancer Metabolism as a Sequela

2019 ◽  
Vol 20 (15) ◽  
pp. 3694 ◽  
Author(s):  
Rosa Cardone ◽  
Khalid Alfarouk ◽  
Robert Elliott ◽  
Saad Alqahtani ◽  
Samrein Ahmed ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Biology ◽  
Cancer Metabolism ◽  
Cellular Proliferation ◽  
Cell Metabolism ◽  
Krebs Cycle ◽  
Building Blocks ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Sodium Hydrogen Exchanger

Cancer cells have an unusual regulation of hydrogen ion dynamics that are driven by poor vascularity perfusion, regional hypoxia, and increased glycolysis. All these forces synergize/orchestrate together to create extracellular acidity and intracellular alkalinity. Precisely, they lead to extracellular pH (pHe) values as low as 6.2 and intracellular pH values as high as 8. This unique pH gradient (∆pHi to ∆pHe) across the cell membrane increases as the tumor progresses, and is markedly displaced from the electrochemical equilibrium of protons. These unusual pH dynamics influence cancer cell biology, including proliferation, metastasis, and metabolic adaptation. Warburg metabolism with increased glycolysis, even in the presence of Oxygen with the subsequent reduction in Krebs’ cycle, is a common feature of most cancers. This metabolic reprogramming confers evolutionary advantages to cancer cells by enhancing their resistance to hypoxia, to chemotherapy or radiotherapy, allowing rapid production of biological building blocks that support cellular proliferation, and shielding against damaging mitochondrial free radicals. In this article, we highlight the interconnected roles of dysregulated pH dynamics in cancer initiation, progression, adaptation, and in determining the programming and re-programming of tumor cell metabolism.

scholarly journals REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells

Oncogene ◽  
2003 ◽  
Vol 22 (19) ◽  
pp. 2920-2925 ◽  
Author(s):  
Josien K Oosterhoff ◽  
Fred Penninkhof ◽  
Albert O Brinkmann ◽  
J Anton Grootegoed ◽  
Leen J Blok
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Cells ◽  
Growth Factor Signalling

scholarly journals An evolutionarily conserved enzyme degrades transforming growth factor-alpha as well as insulin.

1989 ◽  
Vol 109 (3) ◽  
pp. 1301-1307 ◽  
Author(s):  
J V Garcia ◽  
B D Gehm ◽  
M R Rosner
Keyword(s):  
Growth Factor ◽  
Mammalian Cells ◽  
Transforming Growth Factor ◽  
Physiological Role ◽  
Evolutionary Conservation ◽  
Transforming Growth Factor Alpha ◽  
Evolutionarily Conserved ◽  
Factor Alpha ◽  
Single Enzyme

A single enzyme found in both Drosophila and mammalian cells is able to selectively bind and degrade transforming growth factor (TGF)-alpha and insulin, but not EGF, at physiological concentrations. These growth factors are also able to inhibit binding and degradation of one another by the enzyme. Although there are significant immunological differences between the mammalian and Drosophila enzymes, the substrate specificity has been highly conserved. These results demonstrate the existence of a selective TGF-alpha-degrading enzyme in both Drosophila and mammalian cells. The evolutionary conservation of the ability to degrade both insulin and TGF-alpha suggests that this property is important for the physiological role of the enzyme and its potential for regulating growth factor levels.

scholarly journals More Than Meets the Eye Regarding Cancer Metabolism

2021 ◽  
Vol 22 (17) ◽  
pp. 9507
Author(s):  
Anna Kubicka ◽  
Karolina Matczak ◽  
Magdalena Łabieniec-Watała
Keyword(s):  
Cancer Cells ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Cancer Therapies ◽  
High Demand ◽  
Normal Cells ◽  
Regulatory Changes ◽  
The Difference ◽  
New Treatment ◽  
Atp Supply

In spite of the continuous improvement in our knowledge of the nature of cancer, the causes of its formation and the development of new treatment methods, our knowledge is still incomplete. A key issue is the difference in metabolism between normal and cancer cells. The features that distinguish cancer cells from normal cells are the increased proliferation and abnormal differentiation and maturation of these cells, which are due to regulatory changes in the emerging tumour. Normal cells use oxidative phosphorylation (OXPHOS) in the mitochondrion as a major source of energy during division. During OXPHOS, there are 36 ATP molecules produced from one molecule of glucose, in contrast to glycolysis which provides an ATP supply of only two molecules. Although aerobic glucose metabolism is more efficient, metabolism based on intensive glycolysis provides intermediate metabolites necessary for the synthesis of nucleic acids, proteins and lipids, which are in constant high demand due to the intense cell division in cancer. This is the main reason why the cancer cell does not “give up” on glycolysis despite the high demand for energy in the form of ATP. One of the evolving trends in the development of anti-cancer therapies is to exploit differences in the metabolism of normal cells and cancer cells. Currently constructed therapies, based on cell metabolism, focus on the attempt to reprogram the metabolic pathways of the cell in such a manner that it becomes possible to stop unrestrained proliferation.

scholarly journals Fibroblasts as Modulators of Local and Systemic Cancer Metabolism

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 619 ◽  
Author(s):  
Hannah Sanford-Crane ◽  
Jaime Abrego ◽  
Mara H. Sherman
Keyword(s):  
Wound Healing ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Response To Therapy ◽  
Metabolic Functions ◽  
Autonomous Regulation ◽  
Wound Healing Response ◽  
Metastatic Capacity ◽  
Cancer Cell Metabolism ◽  
Fibroblastic Cells

Fibroblast activation is an accompanying feature of solid tumor progression, resembling a conserved host response to tissue damage. Cancer-associated fibroblasts (CAFs) comprise a heterogeneous and plastic population with increasingly appreciated roles in tumor growth, metastatic capacity, and response to therapy. Classical features of fibroblasts in a wound-healing response, including profound extracellular matrix production and cytokine release, are recapitulated in cancer. Emerging evidence suggests that fibroblastic cells in the microenvironments of solid tumors also critically modulate cellular metabolism in the neoplastic compartment through mechanisms including paracrine transfer of metabolites or non-cell-autonomous regulation of metabolic signaling pathways. These metabolic functions may represent common mechanisms by which fibroblasts stimulate growth of the regenerating epithelium during a wound-healing reaction, or may reflect unique co-evolution of cancer cells and surrounding stroma within the tumor microenvironment. Here we review the recent literature supporting an important role for CAFs in regulation of cancer cell metabolism, and relevant pathways that may serve as targets for therapeutic intervention.

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