PXD015122-3

PXD015122 is an original dataset announced via ProteomeXchange.

Title	AKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture
Description	In 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:01:01.973.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	DONGQING ZHENG
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-22 03:00:00	ID requested
1	2020-03-19 07:49:07	announced
2	2020-06-12 03:42:18	announced	2020-06-12: Updated publication reference for PubMed record(s): 32094265.
⏵ 3	2024-10-22 05:01:10	announced	2024-10-22: Updated project metadata.

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]

10.1242/jcs.239277;

submitter keyword: oxidative culture, proteomics, metabolomics, MYC, galactose, catalase, ROS,AKT, oxidative stress, cancer cells survival;

Nicholas A. Graham
contact affiliation	Mork Family Dept. of Chemical Engineering and Material Science, Associate Prof.
contact email	nagraham@usc.edu
lab head
DONGQING ZHENG
contact affiliation	University of Southern California
contact email	zhengd@usc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015122
     1. Label: PRIDE project
     2. Name: AKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture