PXD056858-1

PXD056858 is an original dataset announced via ProteomeXchange.

Title	HSP27 Functional Switch Drives Castration-Resistant Prostate Cancer via mTOR Pathway Activation, Highlighting Promising Combination Therapies to Restore Treatment Sensitivity
Description	Heat shock protein 27 (HSP27) is a multifunctional protein that plays pivotal roles in prostate cancer (PC) progression to a castration-resistant state, known as CRPC. In this study, we identified and analyzed HSP27-protein interaction maps across various prostatic cell models recapitulating different stages of the disease. Our results demonstrate that HSP27 undergoes a functional switch during CRPC progression by expanding its interacting protein network. Moreover, HSP27 appears to be involved in multiple crucial functions in the development of CRPC, including the regulation of the mTOR pathway. HSP27 strongly regulates mTORC1 signaling through multiple targets, including its regulatory subunit RAPTOR, while its effect on mTORC2 is comparatively moderate. It has been shown that HSP27 prevents the proteasomal degradation of RAPTOR. Combining an HSP27 inhibitor OGX-427 (Apatorsen), and mTOR inhibitors (Everolimus, Sapanisertib) demonstrated a strong synergistic anti-tumor effect in CRPC cell lines and enhanced tumor growth suppression in a xenograft model. This study provides new insights into the role of HSP27 in CRPC progression and suggests that combined therapy with an HSP27 inhibitor and mTOR inhibitors could be a promising strategy for treating CRPC.
HostingRepository	PRIDE
AnnounceDate	2026-07-21
AnnouncementXML	Submission_2026-07-21_04:33:17.389.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AUDEBERT Stephane
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-16 08:52:02	ID requested
⏵ 1	2026-07-21 04:33:18	announced

10.1186/s13046-026-03695-6;

Duong QH, Le TK, Tran TT, Audebert S, Camoin L, Nguyen NG, Baboudjian M, Giusiano S, Phan UTT, Zaghdoudi S, Adelaide J, Baylot V, Gleave M, Garrido C, Ta, ï, eb D, Rocchi P, HSP27 functional switch drives castration-resistant prostate cancer via mTOR pathway activation, highlighting promising combination therapies. J Exp Clin Cancer Res, 45(1):(2026) [pubmed]

submitter keyword: AP-MS, LC-MSMS, Castration Resistant Prostate Cancer (CRPC),HSP27, mTOR pathway, interactome

Audebert Stéphane
contact affiliation	Marseille Protéomique, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Institut Paoli-Calmettes, Aix-Marseille University, 13009 Marseille, France
contact email	stephane.audebert@inserm.fr
lab head
AUDEBERT Stephane
contact affiliation	Marseille Proteomic, Centre de Recherche en Cancérologie de Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes, 27 Boulevard Leï Roure CS30059 13273 Marseille Cedex 09 France
contact email	stephane.audebert@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056858
     1. Label: PRIDE project
     2. Name: HSP27 Functional Switch Drives Castration-Resistant Prostate Cancer via mTOR Pathway Activation, Highlighting Promising Combination Therapies to Restore Treatment Sensitivity