Par-4 Downregulation Promotes Breast Cancer Recurrence by Preventing Multinucleation following Targeted Therapy
Menée à l'aide d'un modèle murin et d'échantillons tumoraux prélevés sur des patientes atteintes d'un cancer du sein, cette étude met en évidence des mécanismes par lesquels une sous-expression de Par-4 favorise la récidive d'un cancer du sein après une chimiothérapie
Most deaths from breast cancer result from tumor recurrence, but mechanisms underlying tumor relapse are largely unknown. We now report that Par-4 is downregulated during tumor recurrence and that Par-4 downregulation is necessary and sufficient to promote recurrence. Tumor cells with low Par-4 expression survive therapy by evading a program of Par-4-dependent multinucleation and apoptosis that is otherwise engaged following treatment. Low Par-4 expression is associated with poor response to neoadjuvant chemotherapy and an increased risk of relapse in patients with breast cancer, and Par-4 is downregulated in residual tumor cells that survive neoadjuvant chemotherapy. Our findings identify Par-4-induced multinucleation as a mechanism of cell death in oncogene-addicted cells and establish Par-4 as a negative regulator of breast cancer recurrence.
"Par-4 is downregulated during tumor recurrence in mice
"Par-4 downregulation is necessary and sufficient for mammary tumor recurrence
"Par-4 downregulation promotes survival of residual tumor cells following therapy
"Par-4-induced multinucleation is a mechanism of death in oncogene-addicted cells
http://linkinghub.elsevier.com/retrieve/pii/S1535610813002341 2013