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PXD020871-1

PXD020871 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleInflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer
DescriptionStandard 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.
HostingRepositoryPRIDE
AnnounceDate2022-02-08
AnnouncementXMLSubmission_2022-02-08_02:48:08.380.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAdele Nicolas
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated lysine; monoacetylated residue; monohydroxylated residue; 2-pyrrolidone-5-carboxylic acid (Pro); monohydroxylated proline; iodoacetamide derivatized residue; deamidated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-08-12 06:42:51ID requested
12022-02-08 02:48:08announced
22023-11-14 08:53:45announced2023-11-14: Updated project metadata.
Publication List
10.1016/J.CCELL.2022.01.004;
Keyword List
submitter keyword: rectal cancer, chemoradiotherapy, extracellular matrix, matrisome, TMT labeling
Contact List
Florian R. Greten
contact affiliationInstitute for Tumor Biology and Experimental Therapy Georg-Speyer-Haus 60596 Frankfurt/Main Germany
contact emailgreten@gsh.uni-frankfurt.de
lab head
Adele Nicolas
contact affiliationInstitute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt/Main, Germany Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt/Main, Germany
contact emailnicolas@gsh.uni-frankfurt.de
dataset submitter
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Dataset FTP location
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