Metabolic Adaptations Alter Metastatic Fitness in Brain-Tropic Breast Cancer

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Geneviève Deblois ◽  
Harvey W. Smith ◽  
Ingrid S. Tam ◽  
Simon-Pierre Gravel ◽  
Maxime Caron ◽  
...  

2017 ◽  
Author(s):  
Mirela Berisa ◽  
Simona Podgrabinska ◽  
Brandon Nicolay ◽  
Raul Mostoslavsky ◽  
Jerry Chipuk ◽  
...  

2020 ◽  
Vol 21 (23) ◽  
pp. 9125
Author(s):  
Sara El-Sahli ◽  
Lisheng Wang

Metabolic reprogramming of cancer is now considered a hallmark of many malignant tumors, including breast cancer, which remains the most commonly diagnosed cancer in women all over the world. One of the main challenges for the effective treatment of breast cancer emanates from the existence of a subpopulation of tumor-initiating cells, known as cancer stem cells (CSCs). Over the years, several pathways involved in the regulation of CSCs have been identified and characterized. Recent research has also shown that CSCs are capable of adopting a metabolic flexibility to survive under various stressors, contributing to chemo-resistance, metastasis, and disease relapse. This review summarizes the links between the metabolic adaptations of breast cancer cells and CSC-associated pathways. Identification of the drivers capable of the metabolic rewiring in breast cancer cells and CSCs and the signaling pathways contributing to metabolic flexibility may lead to the development of effective therapeutic strategies. This review also covers the role of these metabolic adaptation in conferring drug resistance and metastasis in breast CSCs.


2018 ◽  
Author(s):  
Geneviève Deblois ◽  
Seyed Ali Madani Tonekaboni ◽  
Yunchi Ingrid Kao ◽  
Felicia Tai ◽  
Xiaojing Liu ◽  
...  

SUMMARYCancer cell survival upon cytotoxic drug exposure leads to changes in cell identity, dictated by the epigenome. Several metabolites serve as substrates or co-factors to chromatin-modifying enzymes, suggesting that metabolic changes can underlie change in cell fate. Here, we show that progression of triple-negative breast cancer (TNBC) to taxane-resistance is characterized by altered methionine metabolism and S-adenosylmethionine (SAM) availability, giving rise to DNA hypomethylation in regions enriched for transposable elements (TE). Compensatory redistribution of H3K27me3 forming Large Organized Chromatin domains of lysine (K) modification (LOCK) prevents expression of TE in taxane-resistant cells. Pharmacological inhibition of EZH2, the H3K27me3 methyltransferase, alleviates TE repression, leading to the accumulation of dsRNA and activation of the interferon viral mimicry-response, specifically inhibiting the growth of taxane-resistant TNBC. Together, our work delineates a role for metabolic adaptations in redefining the epigenome of taxane-resistant TNBC cells and underlies an epigenetic vulnerability toward pharmacological inhibition of EZH2.


EBioMedicine ◽  
2018 ◽  
Vol 37 ◽  
pp. 144-157 ◽  
Author(s):  
Jose M. Ayuso ◽  
Amani Gillette ◽  
Karina Lugo-Cintrón ◽  
Suehelay Acevedo-Acevedo ◽  
Ismael Gomez ◽  
...  

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Shawn McGuirk ◽  
Yannick Audet-Delage ◽  
Matthew G Annis ◽  
Yibo Xue ◽  
Mathieu Vernier ◽  
...  

Chemotherapy resistance is a critical barrier in cancer treatment. Metabolic adaptations have been shown to fuel therapy resistance; however, little is known regarding the generality of these changes and whether specific therapies elicit unique metabolic alterations. Using a combination of metabolomics, transcriptomics, and functional genomics, we show that two anthracyclines, doxorubicin and epirubicin, elicit distinct primary metabolic vulnerabilities in human breast cancer cells. Doxorubicin-resistant cells rely on glutamine to drive oxidative phosphorylation and de novo glutathione synthesis, while epirubicin-resistant cells display markedly increased bioenergetic capacity and mitochondrial ATP production. The dependence on these distinct metabolic adaptations is revealed by the increased sensitivity of doxorubicin-resistant cells and tumor xenografts to buthionine sulfoximine (BSO), a drug that interferes with glutathione synthesis, compared with epirubicin-resistant counterparts that are more sensitive to the biguanide phenformin. Overall, our work reveals that metabolic adaptations can vary with therapeutics and that these metabolic dependencies can be exploited as a targeted approach to treat chemotherapy-resistant breast cancer.


2018 ◽  
Author(s):  
Jose Ayuso ◽  
Amani Gillette ◽  
Karina Lugo-Cintrón ◽  
Suehelay Acevedo-Acevedo ◽  
Ismael Gomez ◽  
...  

Author(s):  
G. Kasnic ◽  
S. E. Stewart ◽  
C. Urbanski

We have reported the maturation of an intracisternal A-type particle in murine plasma cell tumor cultures and three human tumor cell cultures (rhabdomyosarcoma, lung adenocarcinoma, and osteogenic sarcoma) after IUDR-DMSO activation. In all of these studies the A-type particle seems to develop into a form with an electron dense nucleoid, presumably mature, which is also intracisternal. A similar intracisternal A-type particle has been described in leukemic guinea pigs. Although no biological activity has yet been demonstrated for these particles, on morphologic grounds, and by the manner in which they develop within the cell, they may represent members of the same family of viruses.


Author(s):  
John L. Swedo ◽  
R. W. Talley ◽  
John H. L. Watson

Since the report, which described the ultrastructure of a metastatic nodule of human breast cancer after estrogen therapy, additional ultrastructural observations, including some which are correlative with pertinent findings in the literature concerning mycoplasmas, have been recorded concerning the same subject. Specimen preparation was identical to that in.The mitochondria possessed few cristae, and were deteriorated and vacuolated. They often contained particulates and fibrous structures, sometimes arranged in spindle-shaped bundles, Fig. 1. Another apparent aberration was the occurrence, Fig. 2 (arrows) of linear profiles of what seems to be SER, which lie between layers of RER, and are often recognizably continuous with them.It was noted that the structure of the round bodies, interpreted as within autophagic vacuoles in the previous communication, and of vesicular bodies, described morphologically closely resembled those of some mycoplasmas. Specifically, they simulated or reflected the various stages of replication reported for mycoplasmas grown on solid nutrient. Based on this observation, they are referred to here as “mycoplasma-like” structures, in anticipation of confirmatory evidence from investigations now in progress.


2010 ◽  
Vol 34 (8) ◽  
pp. S49-S49
Author(s):  
Lei Wang ◽  
Xun Zhou ◽  
Lihong Zhou ◽  
Yong Chen ◽  
Xun Zhu ◽  
...  

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