PXD023626 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Paradoxical drug sensitization of lung cancer cells by stromal fibroblast-secreted IGF-binding proteins: Secretomics |
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_08:15:34.078.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD023626 |
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 | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-01-15 09:07:04 | ID requested | |
1 | 2023-03-10 19:07:40 | announced | |
⏵ 2 | 2023-11-14 08:15:35 | announced | 2023-11-14: Updated project metadata. |
Publication List
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/PXD023626; |
Keyword List
submitter keyword: Lung Cancer, Secretomics, Fibroblasts, Targeted Therapy |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD023626
- Label: PRIDE project
- Name: Paradoxical drug sensitization of lung cancer cells by stromal fibroblast-secreted IGF-binding proteins: Secretomics