Dataset Information

HSP27 Functional Switch Drives Castration-Resistant Prostate Cancer via mTOR Pathway Activation, Highlighting Promising Combination Therapies to Restore Treatment Sensitivity

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: AUDEBERT Stephane

LAB HEAD: Audebert Stéphane

PROVIDER: PXD056858 | Pride | 2026-07-21

REPOSITORIES: Pride

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HSP27 functional switch drives castration-resistant prostate cancer via mTOR pathway activation, highlighting promising combination therapies.

Duong Quang Hieu QH Le Thi Khanh TK Tran Thi Thom TT Audebert Stéphane S Camoin Luc L Nguyen Ngan Giang NG Baboudjian Michael M Giusiano Sophie S Phan Uyen Thi Tu UTT Zaghdoudi Souhaila S Adelaide José J Baylot Virginie V Gleave Martin M Garrido Carmen C Taïeb David D Rocchi Palma P

Journal of experimental & clinical cancer research : CR 20260325 1

BACKGROUND: Castration-resistant prostate cancer (CRPC) is an advanced and ultimately incurable stage of the disease that arises despite androgen deprivation and remains challenging to treat due to the limited and short-lived efficacy of current therapies. Heat shock protein 27 (HSP27), a molecular chaperone, has been implicated in prostate cancer (PC) progression and therapy resistance; however, its mechanistic roles remain incompletely understood. This study aimed to delineate the HSP27 intera ...[more]

PMID: 41877198

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