scholarly journals The landscape of tiered regulation of breast cancer cell metabolism

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rotem Katzir ◽  
Ibrahim H. Polat ◽  
Michal Harel ◽  
Shir Katz ◽  
Carles Foguet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Metabolic Regulation ◽  
Cell Metabolism ◽  
Cancer Cell Line ◽  
Hierarchical Organization ◽  
Metabolic Reprogramming ◽  
A Genome ◽  
Cancer Cell Metabolism

AbstractAltered metabolism is a hallmark of cancer, but little is still known about its regulation. In this study, we measure transcriptomic, proteomic, phospho-proteomic and fluxomics data in a breast cancer cell-line (MCF7) across three different growth conditions. Integrating these multiomics data within a genome scale human metabolic model in combination with machine learning, we systematically chart the different layers of metabolic regulation in breast cancer cells, predicting which enzymes and pathways are regulated at which level. We distinguish between two types of reactions, directly and indirectly regulated. Directly-regulated reactions include those whose flux is regulated by transcriptomic alterations (~890) or via proteomic or phospho-proteomics alterations (~140) in the enzymes catalyzing them. We term the reactions that currently lack evidence for direct regulation as (putative) indirectly regulated (~930). Many metabolic pathways are predicted to be regulated at different levels, and those may change at different media conditions. Remarkably, we find that the flux of predicted indirectly regulated reactions is strongly coupled to the flux of the predicted directly regulated ones, uncovering a tiered hierarchical organization of breast cancer cell metabolism. Furthermore, the predicted indirectly regulated reactions are predominantly reversible. Taken together, this architecture may facilitate rapid and efficient metabolic reprogramming in response to the varying environmental conditions incurred by the tumor cells. The approach presented lays a conceptual and computational basis for mapping metabolic regulation in additional cancers.

scholarly journals Collagen density modulates triple-negative breast cancer cell metabolism through adhesion-mediated contractility

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Emma J. Mah ◽  
Austin E. Y. T. Lefebvre ◽  
Gabrielle E. McGahey ◽  
Albert F. Yee ◽  
Michelle A. Digman
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Metabolism ◽  
Cancer Cell Metabolism ◽  
Collagen Density

scholarly journals Autofluorescence flow sorting of breast cancer cell metabolism

2016 ◽  
Vol 10 (8) ◽  
pp. 1026-1033 ◽  
Author(s):  
Amy T. Shah ◽  
Taylor M. Cannon ◽  
James N. Higginbotham ◽  
Robert J. Coffey ◽  
Melissa C. Skala
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Metabolism ◽  
Flow Sorting ◽  
Cancer Cell Metabolism

Docosahexaenoic acid attenuates breast cancer cell metabolism and the Warburg phenotype by targeting bioenergetic function

2014 ◽  
Vol 54 (9) ◽  
pp. 810-820 ◽  
Author(s):  
Michael Mouradian ◽  
Keith D. Kikawa ◽  
Brian P. Dranka ◽  
Steven M. Komas ◽  
Balaraman Kalyanaraman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Docosahexaenoic Acid ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Metabolism ◽  
Cancer Cell Metabolism

scholarly journals GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity

2016 ◽  
Vol 23 (5) ◽  
pp. 567-578 ◽  
Author(s):  
Sharon M. Louie ◽  
Elizabeth A. Grossman ◽  
Lisa A. Crawford ◽  
Lucky Ding ◽  
Roman Camarda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Metabolism ◽  
Cancer Cell Metabolism

scholarly journals 13C and 15N natural isotope abundance reflects breast cancer cell metabolism

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Illa Tea ◽  
Estelle Martineau ◽  
Ingrid Antheaume ◽  
Julie Lalande ◽  
Caroline Mauve ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Metabolism ◽  
Isotope Abundance ◽  
Natural Isotope ◽  
Natural Isotope Abundance ◽  
Cancer Cell Metabolism

scholarly journals Progestins counteract estrogens to shift breast cancer cell metabolism

2020 ◽  
Author(s):  
Ashley V. Ward ◽  
Shawna B. Matthews ◽  
Lynsey M. Fettig ◽  
Jessica Finlay-Schultz ◽  
Peter Kabos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Biology ◽  
Cell Metabolism ◽  
Breast Cancer Cell Lines ◽  
Mitochondrial Morphology ◽  
Cancer Cell Metabolism

Abstract Progesterone receptors (PR) profoundly influence breast cancer biology by modifying estrogen receptor (ER) gene regulation, and, under some contexts, increasing populations of cancer stem cells. Abnormal metabolism is a cancer hallmark that has largely been understudied in relation to hormones in ER+PR+ breast disease. In this study, we investigated how progestins, in the absence or presence of estrogens, affect breast cancer cell metabolism. We measured metabolites using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) in three ER+PR+ breast cancer cell lines (T47D, UCD4, and UCD65) treated with vehicle, estrogen only, progestin only, or the combination. Progestins, in the absence or presence of estrogens, largely downregulated metabolites, particularly those involved in tricarboxylic acid (TCA) cycle and amino acid metabolism. Seahorse metabolic analysis found progestins (alone or plus estrogens) generally shifted cells towards glycolysis with reduced ATP production. Transmission electron microscopy in cell lines and patient-derived xenograft tumors found that estrogens produced an elongated mitochondrial morphology, while estrogen plus progestin treatment reversed this trend. Using the photoconvertible MitoTimer reporter, progestins reduced both baseline and estrogen-induced mitochondrial turnover. Progestins blocked the estrogen-induced expression of mitochondrial biogenesis regulators PGC1α and PGC1β and their downstream targets. These findings indicate that progestins dominantly affect cell metabolism to shift cells to a more glycolytic phenotype with reduced mitochondrial function and amino acid pools; this transition is indicative of less proliferative, but also more dedifferentiated cells. Our results highlight potential benefits and detriments of current clinical studies testing selective PR modulators in ER+ breast cancers.

Abstract 435: Is PYGM dysregulation involved in breast cancer cell metabolism

2014 ◽  
Author(s):  
Veronika SMUTNA ◽  
Maria Vittoria DIECI ◽  
Céline LEFEBVRE ◽  
Véronique SCOTT ◽  
Fabrice ANDRE ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Metabolism ◽  
Cancer Cell Metabolism

scholarly journals Proteinase-activated receptor-2 expression in breast cancer and the role of trypsin on growth and metabolism of breast cancer cell line MDA MB-231

2007 ◽  
pp. 475-484 ◽  
Author(s):  
R Matěj ◽  
P Manďáková ◽  
I Netíková ◽  
P Poučková ◽  
T Olejár
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cell Metabolism ◽  
Cancer Cell Line ◽  
Rt Pcr ◽  
Calcium Mobilization Assay

Proteinase-activated receptor-2 (PAR-2) is a ubiquitous surface molecule participating in many biological processes. It belongs to the family of G protein-coupled receptors activated by the site-specific proteolysis of trypsin and similar proteases. Altered function of PAR-2 has been described in different malignant tumors. In the present study, we investigated the expression of PAR-2 in breast cancer surgical specimens and the role of trypsin in breast cancer cell line MDA MB-231 proliferation and metabolism. A total of 40 surgical samples of infiltrative ductal breast cancer and breast cancer cell line were included in this study. We analyzed PAR-2 expression by immunohistochemistry, RT-PCR and western blot. Activation of PAR-2 on cell line MDA MB-231 was measured using calcium mobilization assay determined by flow cytometry. MTT cell metabolism assay and cell count analysis were used to assess the trypsin influence on breast cancer cell line MDA MB-231 proliferation. Immunohistochemical examination showed the expression of PAR-2 in all samples of breast cancer surgical specimens and high levels of cell lines which was confirmed by RT-PCR and western blot. Calcium mobilization assay corroborated the activation of PAR-2 on cell line MDA MB-231 either by trypsin or by an agonistic peptide. Cell metabolism assay and cell count analysis showed significant differences of proliferative activity of breast cancer cells dependent on the presence or absence of trypsin and serum in the culture medium. PAR-2 is expressed by high levels in infiltrative ductal breast cancer tissue specimens. PAR-2 is also strongly expressed in studied breast cancer cell lines. PAR-2 is activated by trypsin and also by agonistic peptide in the model of breast cancer cell line MDA MB-231. Activation of PAR-2 in vitro influences proliferative and metabolic activity of breast cancer cell line MDA MB-231. The action of trypsin is modified by the presence of serum which is a potential source of protease inhibitors.

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