Abstract:
:Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alters MCF-7 and MDA-MB-231 cell metabolism and promotes proliferation and migration. Since adipocytes are FA-rich, and these FAs are transferred to BrCa cells, we sought to elucidate the FA metabolism of BrCa cells and their response to FA-rich environments. MCF-7 and MDA-MB-231 cells incubated in serum-containing media supplemented with FAs accumulate extracellular FAs as intracellular triacylglycerols (TAG) in a dose-dependent manner, with MDA-MB-231 cells accumulating more TAG. The differences in TAG levels were a consequence of distinct differences in intracellular partitioning of FAs, and not due to differences in the rate of FA uptake. Specifically, MCF-7 cells preferentially partition FAs into mitochondrial oxidation, whereas MDA-MB-231 cells partition FAs into TAG synthesis. These differences in intracellular FA handling underpin differences in the sensitivity to palmitate-induced lipotoxicity, with MDA-MB-231 cells being highly sensitive, whereas MCF-7 cells are partially protected. The attenuation of palmitate-induced lipotoxicity in MCF-7 cells was reversed by inhibition of FA oxidation. Pretreatment of MDA-MB-231 cells with FAs increased TAG synthesis and reduced palmitate-induced apoptosis. Our results provide novel insight into the potential influences of obesity on BrCa biology, highlighting distinct differences in FA metabolism in MCF-7 and MDA-MB-231 cells and how lipid-rich environments modulate these effects.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Balaban S,Lee LS,Varney B,Aishah A,Gao Q,Shearer RF,Saunders DN,Grewal T,Hoy AJdoi
10.1002/1878-0261.12368subject
Has Abstractpub_date
2018-09-01 00:00:00pages
1623-1638issue
9eissn
1574-7891issn
1878-0261journal_volume
12pub_type
杂志文章abstract::As treatment options for patients with incurable metastatic castration-resistant prostate cancer (mCRPC) are considerably limited, novel effective therapeutic options are needed. Checkpoint kinase 1 (CHK1) is a highly conserved protein kinase implicated in the DNA damage response (DDR) pathway that prevents the accumu...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12756
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abstract::Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylatio...
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doi:10.1002/1878-0261.12871
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journal_title:Molecular oncology
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doi:10.1016/j.molonc.2009.05.005
更新日期:2009-08-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1016/j.molonc.2016.06.006
更新日期:2016-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/1878-0261.12812
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12648
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12450
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journal_title:Molecular oncology
pub_type: 临床试验,杂志文章
doi:10.1002/1878-0261.12025
更新日期:2017-02-01 00:00:00
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更新日期:2020-12-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2011.01.002
更新日期:2011-04-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2015.12.005
更新日期:2016-03-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.013
更新日期:2015-04-01 00:00:00
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更新日期:2018-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.molonc.2014.01.009
更新日期:2014-05-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1002/1878-0261.12489
更新日期:2019-06-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.06.008
更新日期:2014-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/1878-0261.12070
更新日期:2017-08-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.05.004
更新日期:2015-11-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12799
更新日期:2020-09-13 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.04.004
更新日期:2014-10-01 00:00:00