PXD038958-1

PXD038958 is an original dataset announced via ProteomeXchange.

Title	Spatial SILAC Regorafenib Treated Bottom-up Proteomic Analysis
Description	Developing effective model systems to evaluate new potential chemotherapeutic reagents is critical. Three-dimensional cell cultures, such as spheroids, aid in bridging the gap between commonly used monolayer cell cultures and significantly more complex and expensive animal models. Spheroid model systems contain pathophysiological and chemical gradients similar to an in vivo tumor, which ultimately form distinct cellular subpopulations. In the spatial SILAC model, labels are pulsed into the spheroid at discrete time windows during development. These media pulses result in labeled proteins in distinct regions of the spheroid, which allows for tracing of quantitative proteomic changes to be correlated to different cellular subregions. In this study, we use the Spatial SILAC model to evaluate the proteomic response of a colon carcinoma spheroid to the multikinase inhibitor Regorafenib. We determined regorafenib to be an effective kinase inhibitor which significantly altered whole spheroid proliferation and resulted in increased apoptosis when the signal was averaged for all cells in the culture. However, when regorafenib treatment is more closely examined among the cellular subpopulations, drastic differences are observed for how the drug impacted the proteome of the necrotic spheroid core and the proliferating outer regions. Whole spheroid and outer region analysis shows that regorafenib treatment inhibited critical pathways such as mTOR signaling, ERK/MAPK signaling, and colorectal cancer metastasis signaling. However, analysis of the core shows that regorafenib had an entirely different effect, including upregulation of MAPK1 and KRAS, possibly indicating drug resistance within these late apoptotic cells. Ultimately, these combinatory studies can be used to further understanding of drug metabolism is different cellular subpopulations and provide valuable information to ultimately improve the accuracy of therapeutic testing.
HostingRepository	PRIDE
AnnounceDate	2024-08-09
AnnouncementXML	Submission_2024-08-09_05:42:47.250.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicole Beller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C labeled residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-19 15:53:52	ID requested
⏵ 1	2024-08-09 05:42:48	announced
2	2024-10-22 06:54:00	announced	2024-10-22: Updated project metadata.

Beller NC, Wang Y, Hummon AB, Evaluating the Pharmacokinetics and Pharmacodynamics of Chemotherapeutics within a Spatial SILAC-Labeled Spheroid Model System. Anal Chem, 95(30):11263-11272(2023) [pubmed]

10.1021/acs.analchem.3c00905;

submitter keyword: Spatial SILAC, Regorafenib, Spheroids

Dr. Amanda Hummon
contact affiliation	Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States
contact email	hummon.1@osu.edu
lab head
Nicole Beller
contact affiliation	The Ohio State University
contact email	beller.25@osu.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/08/PXD038958

PRIDE project URI

• PRIDE
  1. PXD038958
     1. Label: PRIDE project
     2. Name: Spatial SILAC Regorafenib Treated Bottom-up Proteomic Analysis