Metabolomics Analysis of Triple Negative Breast Cancer (BCa) Cell Lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Cells
DISEASE(S): Cancer
PROVIDER: ST000442 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
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| mwtab | Other |
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Project description:We analyzed the transcriptome of two different triple negative breast cancer (TNBC) cell lines to define a comprehensive list of Wnt target genes. Cells were treated with Wnt3a for 6h, 12h or 24h. We found up-regulated and down-regulated genes in response to Wnt3a treatment. They are involved in the Wnt pathway itself, and also in TGFß, p53 and Hedgehog pathways. Thorough characterization of these novel potential Wnt target genes may reveal new regulators of the canonical Wnt pathway. The comparison of our list of Wnt target genes with those published in other cellular contexts confirms the notion that Wnt target genes are tissue-, cell line- and treatment-specific. Cells were seeded in six-well plates, serum starved overnight then treated with Wnt3a for the indicated times (6, 12 and 24 hours). Triplicates for each condition were included in the experiment.
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Project description:We analysed aquired chemotherapeutic resistance of two different triple negative breast cancer cell lines BT-549 (Doxorubicin resistance) and MDA-MB-468 (5-Fluorouracil) by comparing the proteome of the parental cell line with the resistant cell line.
2018-02-23 | PXD008522 | Pride
Project description:Triple negative breast cancer (TNBC) is currently associated with a lack of treatment options. Arsenic derivatives have shown antitumoral activity both in vitro and in vivo; however, their mode of action is not completely understood. In this work we evaluate the response to arsenate of the double positive MCF-7 breast cancer cell line as well as of two different TNBC cell lines, Hs578T and MDA-MB-231. Multimodal experiments were conducted to this end, using functional assays and microarrays. Arsenate was found to induce cytoskeletal alteration, autophagy and apoptosis in TNBC cells, and moderate effects in MCF-7 cells. Gene expression analysis showed that the TNBC cell lines' response to arsenate was more prominent in the G2M checkpoint, autophagy and apoptosis compared to the Human Mammary Epithelial Cells (HMEC) and MCF-7 cell lines. We confirmed the downregulation of anti-apoptotic genes (MCL1, BCL2, TGFβ1 and CCND1) by qRT-PCR, and on the protein level, for TGFβ2, by ELISA. Insight into the mode of action of arsenate in TNBC cell lines it is provided, and we concluded that TNBC and non-TNBC cell lines reacted differently to arsenate treatment in this particular experimental setup. We suggest the future research of arsenate as a treatment strategy against TNBC.
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Project description:Triple-negative breast cancer stands out as the most aggressive subtype of breast malignancy and is characterized by an unfavourable prognosis. Objective: This systematic review summarizes the insights gleaned from metabolomic analyses of individuals afflicted with this cancer variant. The overarching goal was to delineate the molecular alterations associated with triple-negative breast cancer, pinpointing potential therapeutic targets and novel biomarkers. Methods: We systematically searched for evidence using the PubMed database and followed the PRISMA and STARLITE guidelines. The search parameters were delimited to articles published within the last 13 years. Results: From an initial pool of 148 scrutinized articles, 17 studies involving 1686 participants were deemed eligible for inclusion. The current body of research shows a paucity of studies, and the available evidence presents conflicting outcomes. Notwithstanding, Pathway Enrichment Analysis identified the urea and glucose-alanine cycles as the most affected metabolic pathways, followed by arginine, proline, and aspartate metabolism. Conclusion: Future investigations need to focus on elucidating which of those metabolites and/or pathways might be reliable candidates for novel therapeutic interventions or reliable biomarkers for diagnosis and prognosis of this subtype of breast cancer.
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Project description:Triple-negative breast cancer (TNBC) is the most fatal type of breast cancer (BC). Due to the lack of relevant targeted drug therapy, in addition to surgery, chemotherapy is still the most common treatment option for TNBC. TNBC is heterogeneous, and different patients have an unusual sensitivity to chemotherapy. Only part of the patients will benefit from chemotherapy, so neoadjuvant chemotherapy (NAC) is controversial in the treatment of TNBC. Here, we performed an NMR spectroscopy-based metabolomics study to analyze the relationship between the patients' metabolic phenotypes and chemotherapy sensitivity in the serum samples. Metabolic phenotypes from patients with pathological partial response, pathological complete response, and pathological stable disease (pPR, pCR, and pSD) could be distinguished. Furthermore, we conducted metabolic pathway analysis based on identified significant metabolites and revealed significantly disturbed metabolic pathways closely associated with three groups of TNBC patients. We evaluated the discriminative ability of metabolites related to significantly disturbed metabolic pathways by using the multi-receiver-operating characteristic (ROC) curve analysis. Three significantly disturbed metabolic pathways of glycine, serine, and threonine metabolism, valine, leucine, and isoleucine biosynthesis, and alanine, aspartate, and glutamate metabolism could be used as potential predictive models to distinguish three types of TNBC patients. These results indicate that a metabolic phenotype could be used to predict whether a patient is suitable for NAC. Metabolomics research could provide data in support of metabolic phenotypes for personalized treatment of TNBC.
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