EHD2 is a Predictive Biomarker of Chemotherapy Efficacy in Triple Negative Breast Carcinoma

Archive ouverte

Shen, Wei-Wei | Bièche, Ivan | Fuhrmann, Laetitia | Vacher, Sophie | Vincent-Salomon, Anne | Torrino, Stéphanie | Lamaze, Christophe

Edité par CCSD ; Nature Publishing Group -

International audience. EHD2 is a mechanotransducing ATPase localized in caveolae invaginations at the plasma membrane. EHD2 has recently been associated with several human cancers, however the significance of EHD2 transcript levels in cancer prognosis remains debated. Breast cancer is the most commonly occurring cancer in women and prognosis is variable depending on the subtypes. Triple negative breast cancer (TNBC) often has a poor therapeutic response. The aim of this study was to assess the prognostic significance of EHD2 transcripts and protein expression levels in breast carcinomas. We found that low EHD2 levels were associated with enhanced proliferation, migration and invasion of TNBC cells. EHD2 expression was significantly reduced in TNBC tissues and the loss of EHD2 led to higher expression of the pro-tumoral cytokine IL-8. In apparent contradiction with in vitro data, multivariate analysis of two independent cohorts of breast cancer patients revealed that low EHD2 was in fact associated with good prognosis in the highly proliferative TNBC subtype. Accordingly, TNBC low EHD2 expressers were found to benefit the most from chemotherapy when compared to all subtypes of breast cancers. Our study validates EHD2 expression level as an independent prognostic factor of metastasis-free survival and as a new predictive marker of chemotherapy efficacy in TNBC patients.

Suggestions

Du même auteur

EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription

Archive ouverte | Torrino, Stéphanie | CCSD

International audience. Caveolae are small invaginated pits that function as dynamic mechanosensors to buffer tension variations at the plasma membrane. Here we show that under mechanical stress, the EHD2 ATPase is ...

EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription

Archive ouverte | Torrino, Stéphanie | CCSD

International audience. Rockefeller University Press Caveolae are small invaginated pits that function as dynamic mechanosensors to buffer tension variations at the plasma membrane. Here we show that under mechanica...

VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX

Archive ouverte | Bonin, Florian | CCSD

International audience. BACKGROUND:The WW domain-containing oxidoreductase (WWOX) gene, frequently altered in breast cancer, encodes a tumor suppressor whose function is mediated through its interactions with cancer...

Chargement des enrichissements...