PXD023692

PXD023692 is an original dataset announced via ProteomeXchange.

Title	Paradoxical drug sensitization of lung cancer cells by stromal fibroblast-secreted IGF-binding proteins: Phosphotyrosine Profiling
Description	Cancer-associated fibroblasts (CAFs) are an integral part of the tumor microenvironment often linked to drug resistance. Here, we report that CAFs, but not normal fibroblasts, can promote either resistance or unexpected drug sensitization of different lung cancer cells. Using unbiased secretomics, transcriptomics and tyrosine phosphoproteomics, we observed differential expression of several IGF1R signaling components, such as IGF-binding proteins and IGF1/2, and downstream signaling effects on cancer cells by fibroblasts. IGF1/2 treatment or IGFBP5 silencing in CAFs reversed, while addition of exogenous IGFBPs or pharmacological IGF1R inhibitors phenocopied the sensitizing effects. Combining IGF1R and EGFR inhibitors synergized in 2D and 3D models of different drug-resistant and naïve EGFR-mutant lung cancer cells and decreased tumor growth in vivo. These results suggest that multiple resistance mechanisms coexist within the same cancer cells, that CAFs context-dependently cause drug resistance or sensitization, and that understanding both of these differential mechanisms leads to improved therapeutic approaches.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:27:55.885.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD023692
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-20 01:36:41	ID requested
1	2023-03-10 19:07:48	announced
⏵ 2	2023-11-14 08:27:56	announced	2023-11-14: Updated project metadata.

Remsing Rix LL, Sumi NJ, Hu Q, Desai B, Bryant AT, Li X, Welsh EA, Fang B, Kinose F, Kuenzi BM, Chen YA, Antonia SJ, Lovly CM, Koomen JM, Haura EB, Marusyk A, Rix U, IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells. Sci Signal, 15(747):eabj5879(2022) [pubmed]

10.6019/PXD023692;

submitter keyword: Tyrosine Phosphorylation,Lung Cancer, Fibroblasts, Targeted Therapy

Uwe Rix, PhD
contact affiliation	Moffitt Cancer Center Tampa, FL, USA
contact email	uwe.rix@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
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/2023/03/PXD023692

PRIDE project URI

• PRIDE
  1. PXD023692
     1. Label: PRIDE project
     2. Name: Paradoxical drug sensitization of lung cancer cells by stromal fibroblast-secreted IGF-binding proteins: Phosphotyrosine Profiling