Détail du document
Identifiant
doi:10.1186/s12964-023-01441-5...
Auteur
Prokakis, Evangelos Bamahmoud, Husam Jansari, Shaishavi Fritsche, Lena Dietz, Alexander Boshnakovska, Angela Rehling, Peter Johnsen, Steven A. Gallwas, Julia Wegwitz, FlorianLangue
enEditeur
BioMed Central
Catégorie
Life Sciences
Année
2024
Date de référencement
14/02/2024
Mots clés
breast cancer tnbc epigenetics usp22 oxphos cscs therapy resistance role study cancer usp22Résumé
Background Breast cancer (BC) is the most frequent tumor entity in women worldwide with a high chance of therapeutic response in early- and non-metastatic disease stages.
Among all BC subtypes, triple-negative BC (TNBC) is the most challenging cancer subtype lacking effective molecular targets due to the particular enrichment of cancer stem cells (CSCs), frequently leading to a chemoresistant phenotype and metastasis.
The Ubiquitin Specific Peptidase 22 (USP22) is a deubiquitinase that has been frequently associated with a CSC-promoting function and intimately implicated in resistance to conventional therapies, tumor relapse, metastasis and overall poor survival in a broad range of cancer entities, including BC.
To date, though, the role of USP22 in TNBC has been only superficially addressed.
Methods The current study utilized the MMTV-cre, Usp22 ^fl/fl transgenic mouse model to study the involvement of USP22 in the stem cell-like properties of the growing mammary tissue.
Additionally, we combined high-throughput transcriptomic analyses with publicly available patient transcriptomic data and utilized TNBC culture models to decipher the functional role of USP22 in the CSC characteristics of this disease.
Results Interestingly, we identified that USP22 promotes CSC properties and drug tolerance by supporting the oxidative phosphorylation program, known to be largely responsible for the poor response to conventional therapies in this particularly aggressive BC subtype.
Conclusions This study suggests a novel tumor-supportive role of USP22 in sustaining cellular respiration to facilitate the drug-tolerant behavior of HER2^+-BC and TNBC cells.
Therefore, we posit USP22 as a promising therapeutic target to optimize standard therapies and combat the aggressiveness of these malignancies.
Video Abstract
Prokakis, Evangelos,Bamahmoud, Husam,Jansari, Shaishavi,Fritsche, Lena,Dietz, Alexander,Boshnakovska, Angela,Rehling, Peter,Johnsen, Steven A.,Gallwas, Julia,Wegwitz, Florian, 2024, USP22 supports the aggressive behavior of basal-like breast cancer by stimulating cellular respiration, BioMed Central
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