EHD2 is a Predictive Biomarker of Chemotherapy Efficacy in Triple Negative Breast Carcinoma
- Others:
- Membrane Dynamics and Mechanics of Intracellular Signaling team [Paris] ; Institut Curie [Paris]-Université Paris sciences et lettres (PSL)
- Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143) ; Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
- Pharmacogenomics Unit [Paris] ; Department of Genetics [Paris] ; Institut Curie [Paris]-Institut Curie [Paris]
- Department of Pathology [Paris] ; Institut Curie [Paris]
- Unité de génétique et biologie des cancers (U830) ; Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- The Johannes and Lamaze teams, the PICT-IBiSA/Nikon Imaging Centre at Institut Curie-CNRS and the France-BioImaging infrastructure are members of Labex Cell(n)Scale (N° ANR-11-LBX-0038) and of IDEX PSL (N° ANR-10-IDEX-0001-02 PSL).
- ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010)
Description
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.
Abstract
International audience
Additional details
- URL
- https://www.hal.inserm.fr/inserm-02864579
- URN
- urn:oai:HAL:inserm-02864579v1
- Origin repository
- UNICA