PXD020871 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Inflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer |
Description | Standard cancer therapy targets tumor cells without considering the possible collateral damage on the tumor microenvironment that could impair therapy response. Employing patient-derived tumor organoids and primary stroma cells or a novel murine rectal cancer model, we show that interleukin-1 (IL-1 dependent inflammatory cancer-associated fibroblast (iCAF) polarization triggers oxidative DNA damage in iCAFs leading to p53-mediated therapy-induced senescence associated with changes in matrisome composition, chemoradiotherapy resistance and disease progression. IL-1 inhibition, prevention of iCAF senescence or senolytic therapy sensitizes mice to irradiation. In rectal cancer patients a dominant iCAF gene signature as well as lower IL-1 receptor antagonist (IL-1RA) serum levels correlate with poor prognosis. Moreover, conditioned supernatant from patient tumor organoids renders fibroblasts susceptible to radiation-induced senescence in an IL-1-dependent manner. Collectively, we unravel a critical role for iCAFs in therapy resistance and identify IL-1 signaling as an attractive target for stroma-repolarization and prevention of CAF senescence. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:53:44.924.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Adele Nicolas |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated lysine; acetylated residue; monohydroxylated residue; 2-pyrrolidone-5-carboxylic acid (Pro); monohydroxylated proline; deamidated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-08-12 06:42:51 | ID requested | |
1 | 2022-02-08 02:48:08 | announced | |
⏵ 2 | 2023-11-14 08:53:45 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: chemoradiotherapy,rectal cancer, matrisome, TMT labeling, extracellular matrix |
Contact List
Florian R. Greten |
contact affiliation | Institute for Tumor Biology and Experimental Therapy Georg-Speyer-Haus 60596 Frankfurt/Main Germany |
contact email | greten@gsh.uni-frankfurt.de |
lab head | |
Adele Nicolas |
contact affiliation | Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt/Main, Germany Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt/Main, Germany |
contact email | nicolas@gsh.uni-frankfurt.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020871
- Label: PRIDE project
- Name: Inflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer