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PXD015122

PXD015122 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture
DescriptionIn addition to driving tumorigenesis, oncogenes can create metabolic vulnerabilities in cancer cells. Here, we tested how the oncogenes AKT and MYC affect the ability to shift between respiration and glycolysis. Using immortalized mammary epithelial cellsMCF10A, we discovered constitutively active AKT but not MYC induced cell death in galactose culture, where cells must rely on oxidative phosphorylation for energy generation. However, the negative effects of AKT were short-lived, and AKT-expressing cells recommenced growth after ~15 days in galactose culture. To identify the mechanisms regulating AKT-mediated cell death, we first used metabolomics and found that AKT cells dying in galactose culture exhibited upregulated glutathione metabolism. Next, using shotgun proteomics, we discovered AKT cells dying in galactose upregulated proteins related to nonsense-mediated mRNA decay (NMD), a known response to oxidative stress. We therefore measured levels of reactive oxygen species (ROS) and discovered galactose culture induced ROS only in cells expressing AKT. Additionally, we found thatdiscovered the ROS scavenger catalase rescued AKT-expressing cells from galactose culture-induced cell death. We then demonstrated that breast cancer cell lines with constitutively active AKT signaling also exhibited cell death in galactose culture and rescue by catalase. Together, our results demonstrate that AKT but not MYC induces a metabolic vulnerability in cancer cells, namely the that restricted flexibility to use oxidative phosphorylation. 
HostingRepositoryPRIDE
AnnounceDate2020-03-19
AnnouncementXMLSubmission_2020-06-12_03:42:17.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDONGQING ZHENG
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-08-22 03:00:00ID requested
12020-03-19 07:49:07announced
22020-06-12 03:42:18announced2020-06-12: Updated publication reference for PubMed record(s): 32094265.
Publication List
Zheng D, Sussman JH, Jeon MP, Parrish ST, MacMullan MA, Delfarah A, Graham NA, AKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture. J Cell Sci, 133(7):(2020) [pubmed]
Keyword List
submitter keyword: AKT, MYC, proteomics, metabolomics, galactose, oxidative culture, oxidative stress, ROS, catalase, cancer cells survival;
Contact List
Nicholas A. Graham
contact affiliationMork Family Dept. of Chemical Engineering and Material Science, Associate Prof.
contact emailnagraham@usc.edu
lab head
DONGQING ZHENG
contact affiliationUniversity of Southern California
contact emailzhengd@usc.edu
dataset submitter
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