PXD060768

PXD060768 is an original dataset announced via ProteomeXchange.

Title	Engagement of the receptor RAGE at myofiber level is a determinant for muscle wasting in cancer conditions
Description	Cachexia is a highly debilitating multifactorial syndrome affecting more than 50% of patients with advanced cancer. RAGE (receptor for advanced glycation end-products) signaling in mice sustains hallmarks of cancer cachexia (CC), including inflammation, the release of tumor-derived CC factors, and skeletal muscle catabolism. Indeed, mice lacking RAGE (Ager−/− mice) showed delayed loss of muscle mass and strength and dramatically increased survival. Here, we investigated the specific contribution to CC of RAGE expressed at tumor and muscle level by using: i) WT and Ager−/− mice subcutaneously injected with LLC (Lewis lung carcinoma) cell clones stably transfected with full-length (fl) RAGE, RAGEΔcyto (a non-transducing form of RAGE) or empty vector; and, ii) a newly generated tamoxifen-inducible conditional AgermKO mouse model, in which the RAGE gene is selectively deleted in skeletal muscles, injected with LLC cells. We found that: i) modulation of RAGE expression in LLC clones did not alter their cachectic potential; ii) Ager−/− mice did not activate muscle catabolism irrespective of the injected LLC clone, suggesting that RAGE overexpression in the tumor is not sufficient per se to induce muscle atrophy; and, iii) LLC-injected AgermKO mice showed increased survival, maintenance of muscle performance, resistance to the loss of body, muscle mass and performance, and reduced circulating CC factors compared with LLC-bearing control (Agerflox) mice. An increase in hybrid myofibers expressing both slow and fast MyHC isoforms characterized muscles of LLC-AgermKO . Different and unexpected proteomic signatures were found in muscles of tumor-bearing mice in dependence on RAGE expression and thirty-five proteins emerged as modulated in common in LLC/AgermKO and LLC/Ager–/– vs LLC/Agerflox mice suggesting novel mechanisms involved in the resistance against CC. Thus, RAGE engagement at myofiber rather than tumor level is a determinant in sustaining CC. Nevertheless, total ablation of the receptor maximally protects against cancer-induced muscle wasting, indicating that systemic targeting of RAGE might represent a promising strategy to counteract the cachexia syndrome in cancer patients.
HostingRepository	PRIDE
AnnounceDate	2026-05-04
AnnouncementXML	Submission_2026-05-04_04:21:19.145.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcello Manfredi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-13 05:06:35	ID requested
⏵ 1	2026-05-04 04:21:20	announced

10.1002/JCSM.70302;

submitter keyword: Muscle,Mouse, Cancer, Cachexia

Marcello Manfredi
contact affiliation	Biological Mass Spectrometry Lab Department of Translational Medicine (DiMeT) Center for Translational Research on Autoimmune & Allergic Diseases - CAAD University of Piemonte Orientale Corso Trieste 15/A, 28100, Novara, Italy
contact email	marcello.manfredi@uniupo.it
lab head
Marcello Manfredi
contact affiliation	University of Eastern Piedmont
contact email	marcello.manfredi@uniupo.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060768
     1. Label: PRIDE project
     2. Name: Engagement of the receptor RAGE at myofiber level is a determinant for muscle wasting in cancer conditions