PXD023133

PXD023133 is an original dataset announced via ProteomeXchange.

Title	Tumor tissue collection and processing under physioxia allows highly relevant detection of signaling networks and drug sensitivity of cancer cells
Description	Preclinical studies of primary cancer cells are always done after tumors are removed from patients or animals at ambient atmospheric oxygen (O2, ~21%). However, O2 concentrations in organs are in the ~3-10% range, with most tumors in an hypoxic or 1-2% O2 environment in vivo. Although effects of O2 tension on tumor cell characteristics in vitro have been studied, these studies are done only after tumors are first collected and processed in ambient air. Similarly, sensitivity of primary cancer cells to anti-cancer agents is routinely examined at ambient O2. Here, using both mouse models and human cancers, we demonstrate that tumors collected, processed and propagated at physiologic (physioxia) O2 compared to ambient air display very distinct differences in key signaling networks including Lgr5/Wnt, Yap, and Nrf2/Keap1, nuclear reactive oxygen species levels, alternative splicing, and sensitivity to several targeted therapies including PIK3CAalpha-specific and EGFR inhibitors. Significance: Extra-physiologic oxygen shock/stress (EPHOSS), as noted in cells collected/processed under ambient air, has been demonstrated to have significant impact on numbers and engrafting ability of hematopoietic stem cells. We report deleterious effects of EPHOSS on cancer cell behavior and EPHOSS-mediated effects on cancer cells give misleading information on signaling pathway activation that could severely impact the relevance of these findings. Cancer cells under EPHOSS show higher proliferation rate compared to cells under physioxia and thus are sensitive to anti-proliferative agents. Thus, drugs that show effectiveness on cancer cells collected in ambient air and subjected to EPHOSS may not be effective or as relevant in vivo, results that could partially explain the limited clinical translation of laboratory findings. Evaluating cell signaling and effects of drugs on cancer cells under physiologic O2 prior to in vivo studies could substantially reduce cost and aid in drug discovery relevant to the actual physioxia/pathological status of the tumor cells in vivo.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_10:54:50.520.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD023133
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-15 01:41:17	ID requested
⏵ 1	2022-02-16 10:54:52	announced

Kumar B, Adebayo AK, Prasad M, Capitano ML, Wang R, Bhat-Nakshatri P, Anjanappa M, Simpson E, Chen D, Liu Y, Schilder JM, Colter AB, Maguire C, Temm CJ, Sandusky G, Doud EH, Wijeratne AB, Mosley AL, Broxmeyer HE, Nakshatri H, Tumor collection/processing under physioxia uncovers highly relevant signaling networks and drug sensitivity. Sci Adv, 8(2):eabh3375(2022) [pubmed]

submitter keyword: Mouse, tumor, LC-MS/MS

Harikrishna Nakshatri, BVSc., PhD
contact affiliation	Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202. VA Roudebush Medical Center, Indianapolis, IN 46202
contact email	hnakshat@iupui.edu
lab head
Emma Doud
contact affiliation	Indiana University School of Medicine
contact email	edoud@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023133
     1. Label: PRIDE project
     2. Name: Tumor tissue collection and processing under physioxia allows highly relevant detection of signaling networks and drug sensitivity of cancer cells