题    目：Functions of the ERR orphan nuclear receptor in bone and cancer

报告人：Jean-Marc Vanacker，法国CNRS高级研究员

主持人：翁杰敏  教授

时   间：10月29日 14:30-15:30（周二）

地    点：闵行校区bevictor伟德官网534报告厅

报告人简介：Jean-Marc Vanacker 教授，  法国CNRS高级研究员。1993获得巴斯德研究所（里尔）的分子病毒学博士。2007-至今任里昂高师功能基因组学研究所“孤儿核受体生理学”团队领导。

报告内容简介：High expression of the orphan nuclear receptor Estrogen-related receptor (ERR) is associated with poor prognosis and reduced disease-free survival in breast cancer patients. ERR is a key regulator of energy metabolism and angiogenesis. This receptor also increases the metastatic potential of tumor cells suggesting its capacity to regulate cellular migration. Our data show that in the absence of ERR cells are disorientated, display an increased actin network and are unable to form a single large lamellipodium at the migration edge. As a result, directional migration is impaired in ERR-deficient cells, although cell motility and velocity per se are not altered as shown by videomicroscopy analysis. We observed that the stability and activation of RHOA is specifically enhanced in the absence of the receptor. As shown by in situ proximity ligation assays, this leads to a random sub-cellular distribution of the active form of the GTPase. Unbiased transcriptomic and Gene Ontology analyses identified target genes of ERR including TNFAIP1, the inactivation of which molecularly and cellularly phenocopies the absence of ERR. Moreover its reintroduction in ERR-deficient cells restores a normal migratory phenotype, validating the ERR/TNFAIP1/RHOA cascade. This molecular pathway is also conserved in monocyte/macrophages physiological migration controlled by ERR. Our results show that ERR is instrumental in physio-pathological cell migration and that, together with published data, this receptor orchestrates distinct processes increasing the aggressive behavior of cancer cells. Data concerning the functions of ERR in bone will also be presented.