scholarly journals Multifaceted Aspects of Metabolic Plasticity in Human Cholangiocarcinoma: An Overview of Current Perspectives

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 596
Author(s):  
Mirella Pastore ◽  
Giulia Lori ◽  
Alessandra Gentilini ◽  
Maria Letizia Taddei ◽  
Giovanni Di Maira ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Malignant Tumor ◽  
Warburg Effect ◽  
Signaling Networks ◽  
Metabolic Plasticity ◽  
Tumor Onset ◽  
Key Players ◽  
Proliferation And Metastasis

Cholangiocarcinoma (CCA) is a deadly tumor without an effective therapy. Unique metabolic and bioenergetics features are important hallmarks of tumor cells. Metabolic plasticity allows cancer cells to survive in poor nutrient environments and maximize cell growth by sustaining survival, proliferation, and metastasis. In recent years, an increasing number of studies have shown that specific signaling networks contribute to malignant tumor onset by reprogramming metabolic traits. Several evidences demonstrate that numerous metabolic mediators represent key-players of CCA progression by regulating many signaling pathways. Besides the well-known Warburg effect, several other different pathways involving carbohydrates, proteins, lipids, and nucleic acids metabolism are altered in CCA. The goal of this review is to highlight the main metabolic processes involved in the cholangio-carcinogeneis that might be considered as potential novel druggable candidates for this disease.

Inhibitor or promoter? The performance of polysaccharides from Ganoderma lucidum on human tumor cells with different p53 statuses

2016 ◽  
Vol 7 (4) ◽  
pp. 1872-1875 ◽  
Author(s):  
Jue Zhang ◽  
Jun-ming Chen ◽  
Xiao-xia Wang ◽  
Yong-mei Xia ◽  
Steve W. Cui ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Ganoderma Lucidum ◽  
Human Tumor ◽  
Tumor Suppressor Protein ◽  
Human Tumor Cells ◽  
Cancer Cell Growth ◽  
Tumor Suppressor Protein P53

GLPs inhibit cancer cell growth when the tumor suppressor protein p53 is functional but often stimulate cancer cells when p53 is absent.

scholarly journals Cancer metabolism and intervention therapy

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Huakan Zhao ◽  
Yongsheng Li
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Acid Synthesis ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Cancer Therapies ◽  
Proliferation And Metastasis ◽  
Immunosuppressive Microenvironment

AbstractMetabolic reprogramming with heterogeneity is a hallmark of cancer and is at the basis of malignant behaviors. It supports the proliferation and metastasis of tumor cells according to the low nutrition and hypoxic microenvironment. Tumor cells frantically grab energy sources (such as glucose, fatty acids, and glutamine) from different pathways to produce a variety of biomass to meet their material needs via enhanced synthetic pathways, including aerobic glycolysis, glutaminolysis, fatty acid synthesis (FAS), and pentose phosphate pathway (PPP). To survive from stress conditions (e.g., metastasis, irradiation, or chemotherapy), tumor cells have to reprogram their metabolism from biomass production towards the generation of abundant adenosine triphosphate (ATP) and antioxidants. In addition, cancer cells remodel the microenvironment through metabolites, promoting an immunosuppressive microenvironment. Herein, we discuss how the metabolism is reprogrammed in cancer cells and how the tumor microenvironment is educated via the metabolic products. We also highlight potential metabolic targets for cancer therapies.

scholarly journals Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect

2019 ◽  
Author(s):  
Kaitlyn E. Johnson ◽  
Grant Howard ◽  
William Mo ◽  
Michael K. Strasser ◽  
Ernesto A. B. F. Lima ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Growth Kinetics ◽  
Exponential Growth ◽  
Allee Effect ◽  
Growth Models ◽  
Cooperative Behavior ◽  
Cell Densities

AbstractModels of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations from exponential growth only at higher densities due to limited resources such as space and nutrients. However, recent pre-clinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models however, tumor growth data is limited by the lower limit of detection (i.e. a measurable lesion) and confounding variables, such as tumor microenvironment and immune responses may cause and mask deviations from exponential growth models. In this work, we present alternative growth models to investigate the presence of an Allee effect in cancer cells seeded at low cell densities in a controlledin vitrosetting. We propose a stochastic modeling framework to consider the small number of cells in this low-density regime and use the moment approach for stochastic parameter estimation to calibrate the stochastic growth trajectories. We validate the framework on simulated data and apply this approach to longitudinal cell proliferation data of BT-474 luminal B breast cancer cells. We find that cell population growth kinetics are best described by a model structure that considers the Allee effect, in that the birth rate of tumor cells depends on cell number. This indicates a potentially critical role of cooperative behavior among tumor cells at low cell densities with relevance to early stage growth patterns of emerging tumors and relapse.Author SummaryThe growth kinetics of cancer cells at very low cell densities are of utmost clinical importance as the ability of a small number of newly transformed or surviving cells to grow exponentially and thus, to “take off” underlies tumor formation and relapse after treatment. Mathematical models of stochastic tumor cell growth typically assume a stochastic birth-death process of cells impacted by limited nutrients and space when cells reach high density, resulting in the widely accepted logistic growth model. Here we present an in-depth investigation of alternate growth models adopted from ecology to describe potential deviations from a simple cell autonomous birth-death model at low cell densities. We show that our stochastic modeling framework is robust and can be used to identify the underlying structure of stochastic growth trajectories from both simulated and experimental data taken from a controlledin vitrosetting in which we can capture data from the relevant low cell density regime. This work suggests that the assumption of cell autonomous proliferation via a constant exponential growth rate at low cell densities may not be appropriate for all cancer cell growth dynamics. Consideration of cooperative behavior amongst tumor cells in this regime is critical for elucidating strategies for controlling tumor cell growth.

scholarly journals MacroH2A impedes metastatic growth by enforcing a discrete dormancy program in disseminated cancer cells

2021 ◽  
Author(s):  
Dan Sun ◽  
Dan Filipescu ◽  
Dan Hasson ◽  
Deepak K. Singh ◽  
Saul Carcamo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Inflammatory Cytokines ◽  
Inhibition Of Proliferation ◽  
Dormant State ◽  
Metastatic Lesions ◽  
Metastatic Growth ◽  
Proliferation And Metastasis ◽  
Pdx Models

AbstractMacroH2A variants have been associated with tumor suppression through inhibition of proliferation and metastasis, as well as their role in cellular senescence. However, their role in regulating the dormant state of disseminated cancer cells (DCCs) remains unclear. Here we reveal that solitary dormant DCCs display increased levels of macroH2A variants in head and neck squamous cell carcinoma PDX models and patient samples compared to proliferating primary or metastatic lesions. We further demonstrate that microenvironmental and stress adaptive signals such as TGFβ2 and p38α/β, which induce DCC dormancy, upregulate macroH2A expression. Functionally, we find that overexpression of macroH2A variants is sufficient to induce tumor cells into dormancy and notably, inducible expression of the macroH2A2 variant suppresses the growth of DCCs into overt metastasis. However, this dormant state does not require well-characterized dormancy factors such as DEC2 and NR2F1, suggesting alternate pathways. Our transcriptomic analyses reveal that macroH2A2 overexpression inhibits E2F, RAS and MYC signaling programs, while upregulating inflammatory cytokines commonly secreted by senescent cells. Taken together, our results demonstrate that macroH2A2 enforces a stable dormant phenotype in DCCs by activating a select subset of dormancy and senescence genes that limit metastasis initiation.

scholarly journals Methionine Dependence of Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 568 ◽  
Author(s):  
Peter Kaiser
Keyword(s):  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Rapid Growth ◽  
Warburg Effect ◽  
Metabolic Flux ◽  
Metabolic Changes ◽  
Normal Cells ◽  
Methionine Dependence ◽  
The Warburg Effect

Tumorigenesis is accompanied by the reprogramming of cellular metabolism. The shift from oxidative phosphorylation to predominantly glycolytic pathways to support rapid growth is well known and is often referred to as the Warburg effect. However, other metabolic changes and acquired needs that distinguish cancer cells from normal cells have also been discovered. The dependence of cancer cells on exogenous methionine is one of them and is known as methionine dependence or the Hoffman effect. This phenomenon describes the inability of cancer cells to proliferate when methionine is replaced with its metabolic precursor, homocysteine, while proliferation of non-tumor cells is unaffected by these conditions. Surprisingly, cancer cells can readily synthesize methionine from homocysteine, so their dependency on exogenous methionine reflects a general need for altered metabolic flux through pathways linked to methionine. In this review, an overview of the field will be provided and recent discoveries will be discussed.

scholarly journals LncRNA OIP5-AS1 Regulates the Warburg Effect Through miR-124-5p/IDH2/HIF-1α Pathway in Cervical Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Li ◽  
Yan Ma ◽  
Kamalibaike Maerkeya ◽  
Davuti Reyanguly ◽  
Lili Han
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Warburg Effect ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Condition ◽  
Cervical Cancer Cells ◽  
The Warburg Effect

Hypoxia reprogrammed glucose metabolism affects the Warburg effect of tumor cells, but the mechanism is still unclear. Long-chain non-coding RNA (lncRNA) has been found by many studies to be involved in the Warburg effect of tumor cells under hypoxic condition. Herein, we find that lncRNA OIP5-AS1 is up-regulated in cervical cancer tissues and predicts poor 5-years overall survival in cervical cancer patients, and it promotes cell proliferation of cervical cancer cells in vitro and in vivo. Moreover, OIP5-AS1 is a hypoxia-responsive lncRNA and is essential for hypoxia-enhanced glycolysis which is IDH2 or hypoxia inducible factor-1α (HIF-1α) dependent. In cervical cancer cells, OIP5-AS1 promotes IDH2 expression by inhibiting miR-124-5p, and IDH2 promotes the Warburg effect of cervical under hypoxic condition through regulating HIF-1α expression. In conclusion, hypoxia induced OIP5-AS1 promotes the Warburg effect through miR-124-5p/IDH2/HIF-1α pathway in cervical cancer.

scholarly journals Do malignant cells sleep at night?

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Luis Enrique Cortés-Hernández ◽  
Zahra Eslami-S ◽  
Antoine M. Dujon ◽  
Mathieu Giraudeau ◽  
Beata Ujvari ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Progression ◽  
Liquid Biopsy ◽  
Biological Rhythms ◽  
Clinical Implications ◽  
Malignant Cells ◽  
Metastatic Cascade ◽  
Key Players

AbstractBiological rhythms regulate the biology of most, if not all living creatures, from whole organisms to their constitutive cells, their microbiota, and also parasites. Here, we present the hypothesis that internal and external ecological variations induced by biological cycles also influence or are exploited by cancer cells, especially by circulating tumor cells, the key players in the metastatic cascade. We then discuss the possible clinical implications of the effect of biological cycles on cancer progression, and how they could be exploited to improve and standardize methods used in the liquid biopsy field.

scholarly journals Calcitriol Suppresses Warburg Effect and Cell Growth in Human Colorectal Cancer Cells

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 963
Author(s):  
Chun-Yin Huang ◽  
Yu-Ting Weng ◽  
Po-Chen Li ◽  
Nien-Tsu Hsieh ◽  
Chun-I Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Warburg Effect ◽  
Active Form ◽  
Biologically Active ◽  
Human Colorectal Cancer ◽  
Colorectal Cancer Cells ◽  
Human Colorectal Cancer Cells

Increasing lines of evidence indicate that the biologically active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D3), prevents cancer progression by reducing cell proliferation, increasing cell differentiation, and inhibiting angiogenesis, among other potential roles. Cancer cells in solid tumors preferably undergo the “Warburg effect” to support cell growth by upregulating glycolysis, and the glycolytic intermediates further serve as building blocks to generate biomass. The objective of the current study is to investigate whether calcitriol affects glucose metabolism and cell growth in human colorectal cancer cells. Calcitriol reduced the expression of cyclin D1 and c-Myc. In addition, calcitriol reduced the expression of glucose transporter 1 (GLUT1) and key glycolytic enzymes and decreased extracellular acidification rate but increased oxygen consumption rate in human colorectal cancer cells. In a subcutaneous HT29 xenograft NOD/SCID mouse model, the volume and weight of the tumors were smaller in the calcitriol groups as compared with the control group, and the expression levels of GLUT1 and glycolytic enzymes, hexokinase 2 and lactate dehydrogenase A, were also lower in the calcitriol groups in a dose-responsive manner. Our data indicate that calcitriol suppresses glycolysis and cell growth in human colorectal cancer cells, suggesting an inhibitory role of the biologically active form of vitamin D in colorectal cancer progression.

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