title: PELO negatively regulates HER receptor signalling and metastasis.
abstract: The HER family is composed of four receptor tyrosine kinases, which are frequently deregulated in several types of cancer. Activated HER receptors initiate intracellular signalling pathways by attracting to the plasma membrane a plethora of adaptor and signalling molecules. Although there are more than a dozen HER-interacting proteins that regulate signal transduction and have been extensively studied, recent proteomic studies have shown the existence of many novel but largely uncharacterized factors that may bind HER receptors. In this report, we describe a cell-based identification of several new HER2-binding proteins, including HAX1, YWHAZ, PELO and ACP1. Analysis of these factors showed that one of them, PELO, binds to active HER2 and epidermal growth factor receptor and thereby attenuates phosphatidylinositol 3-kinase (PI3K)/AKT signalling, likely through regulation of the recruitment of p85-PI3K to activated receptor. Functional characterization of PELO showed that it negatively regulates cell migration and metastasis in vivo. These results reveal that PELO is a novel regulator of HER-signalling and therefore is likely to have a role in inhibiting tumour progression and invasion.
authors: Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors: K
authors: K
authors: Pedersen
authors: Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors: F
authors: F
authors: Canals
authors: Translational Genomics Research Program, VHIO, Barcelona, Spain.
authors: A
authors: A
authors: Prat
authors: Clinical Research Program, VHIO, Barcelona, Spain.
authors: J
authors: J
authors: Tabernero
authors: 1] Preclinical Research Program, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain [2] Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain [3] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors: J
authors: J
authors: Arribas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004720:Endonucleases; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics*; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004720:Endonucleases; D066246:ErbB Receptors; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; C104759:HAX1 protein, human; C508053:ERBB2 protein, human; C550527:pelo protein, human