Matches in SemOpenAlex for { <https://semopenalex.org/work/W2015360869> ?p ?o ?g. }
- W2015360869 endingPage "42" @default.
- W2015360869 startingPage "33" @default.
- W2015360869 abstract "Cancer cells adapt to high levels of oxidative stress in order to survive and proliferate by activating key transcription factors. One such master regulator, the redox sensitive transcription factor NF E2 Related Factor 2 (NRF2), controls the expression of cellular defense genes including those encoding intracellular redox-balancing proteins involved in glutathione (GSH) synthesis. Under basal conditions, Kelch-like ECH-associated protein 1 (KEAP1) targets NRF2 for ubiquitination. In response to oxidative stress, NRF2 dissociates from KEAP1, entering the nucleus and binding to the antioxidant response element (ARE) in the promoter of its target genes. Elevated reactive oxygen species (ROS) production may deplete GSH levels within cancer cells. System xc−, an antiporter that exports glutamate while importing cystine to be converted into cysteine for GSH synthesis, is upregulated in cancer cells in response to oxidative stress. Here, we provided evidence that the expression of xCT, the light chain subunit of system xc−, is regulated by NRF2 in representative human breast cancer cells. Hydrogen peroxide (H2O2) treatment increased nuclear translocation of NRF2, also increasing levels of xCT mRNA and protein and extracellular glutamate release. Overexpression of NRF2 up-regulated the activity of the xCT promoter, which contains a proximal ARE. In contrast, overexpression of KEAP1 repressed promoter activity and decreased xCT protein levels, while siRNA knockdown of KEAP1 up-regulated xCT protein levels and transporter activity. These results demonstrate the importance of the KEAP1/NRF2 pathway in balancing oxidative stress in breast cancer cells through system xc−. We have previously shown that xCT is upregulated in various cancer cell lines under oxidative stress. In the current investigation, we focused on MCF-7 cells as a model for mechanistic studies." @default.
- W2015360869 created "2016-06-24" @default.
- W2015360869 creator A5030230169 @default.
- W2015360869 creator A5048880303 @default.
- W2015360869 creator A5080147776 @default.
- W2015360869 creator A5089229108 @default.
- W2015360869 date "2015-08-01" @default.
- W2015360869 modified "2023-10-05" @default.
- W2015360869 title "Expression of xCT and activity of system xc− are regulated by NRF2 in human breast cancer cells in response to oxidative stress" @default.
- W2015360869 cites W1563428629 @default.
- W2015360869 cites W1572853479 @default.
- W2015360869 cites W1584059416 @default.
- W2015360869 cites W1640681118 @default.
- W2015360869 cites W1789875395 @default.
- W2015360869 cites W1809723326 @default.
- W2015360869 cites W1942154378 @default.
- W2015360869 cites W1965571310 @default.
- W2015360869 cites W1969524738 @default.
- W2015360869 cites W1969675630 @default.
- W2015360869 cites W1971090593 @default.
- W2015360869 cites W1972793256 @default.
- W2015360869 cites W1974546855 @default.
- W2015360869 cites W1974796205 @default.
- W2015360869 cites W1975218333 @default.
- W2015360869 cites W1975803898 @default.
- W2015360869 cites W1976955003 @default.
- W2015360869 cites W1978895733 @default.
- W2015360869 cites W1983899284 @default.
- W2015360869 cites W1988605167 @default.
- W2015360869 cites W1991039871 @default.
- W2015360869 cites W1992564925 @default.
- W2015360869 cites W1999447004 @default.
- W2015360869 cites W2004740124 @default.
- W2015360869 cites W2006911621 @default.
- W2015360869 cites W2013805538 @default.
- W2015360869 cites W2014906740 @default.
- W2015360869 cites W2018593601 @default.
- W2015360869 cites W2018644669 @default.
- W2015360869 cites W2019308992 @default.
- W2015360869 cites W2023560077 @default.
- W2015360869 cites W2025251808 @default.
- W2015360869 cites W2025441849 @default.
- W2015360869 cites W2026987279 @default.
- W2015360869 cites W2027085316 @default.
- W2015360869 cites W2027363510 @default.
- W2015360869 cites W2028673321 @default.
- W2015360869 cites W2043281296 @default.
- W2015360869 cites W2051482314 @default.
- W2015360869 cites W2053047691 @default.
- W2015360869 cites W2054330377 @default.
- W2015360869 cites W2056056906 @default.
- W2015360869 cites W2064769568 @default.
- W2015360869 cites W2075625473 @default.
- W2015360869 cites W2080292234 @default.
- W2015360869 cites W2084063309 @default.
- W2015360869 cites W2085008931 @default.
- W2015360869 cites W2086831475 @default.
- W2015360869 cites W2094961464 @default.
- W2015360869 cites W2107772632 @default.
- W2015360869 cites W2112119764 @default.
- W2015360869 cites W2114101650 @default.
- W2015360869 cites W2122945543 @default.
- W2015360869 cites W2123627658 @default.
- W2015360869 cites W2126163147 @default.
- W2015360869 cites W2133041720 @default.
- W2015360869 cites W2134974848 @default.
- W2015360869 cites W2135889730 @default.
- W2015360869 cites W2143366283 @default.
- W2015360869 cites W2147924866 @default.
- W2015360869 cites W2161432809 @default.
- W2015360869 cites W2161446823 @default.
- W2015360869 cites W2161982997 @default.
- W2015360869 cites W2162437590 @default.
- W2015360869 cites W2164788576 @default.
- W2015360869 cites W2165129832 @default.
- W2015360869 cites W2166291119 @default.
- W2015360869 cites W2168395641 @default.
- W2015360869 cites W2281114779 @default.
- W2015360869 cites W2327068644 @default.
- W2015360869 doi "https://doi.org/10.1016/j.redox.2015.03.003" @default.
- W2015360869 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4392061" @default.
- W2015360869 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25827424" @default.
- W2015360869 hasPublicationYear "2015" @default.
- W2015360869 type Work @default.
- W2015360869 sameAs 2015360869 @default.
- W2015360869 citedByCount "178" @default.
- W2015360869 countsByYear W20153608692015 @default.
- W2015360869 countsByYear W20153608692016 @default.
- W2015360869 countsByYear W20153608692017 @default.
- W2015360869 countsByYear W20153608692018 @default.
- W2015360869 countsByYear W20153608692019 @default.
- W2015360869 countsByYear W20153608692020 @default.
- W2015360869 countsByYear W20153608692021 @default.
- W2015360869 countsByYear W20153608692022 @default.
- W2015360869 countsByYear W20153608692023 @default.
- W2015360869 crossrefType "journal-article" @default.
- W2015360869 hasAuthorship W2015360869A5030230169 @default.
- W2015360869 hasAuthorship W2015360869A5048880303 @default.