title: Coordinated expression of Pax-5 and FAK1 in metastasis.
abstract: The Pax-5 gene encodes a B-cell-specific activator protein (BSAP) that plays a key role in B lymphocyte differentiation and embryogenesis. The deregulation of this transcription factor is also linked to B cell malignancies and recently to other cancers. More specifically, the downstream effects of Pax-5 promote cell-cell interactions and mediate the activation of adhesion genes which result in an epithelial phenotypic behavior of human carcinoma cells. To gain a better understanding of Pax-5-mediated gene regulation, we studied available gene expression data in depth and identified several Pax-5 downstream targets. Among these, we found that Pax-5 activity is consistently inversely correlated with the expression of Focal Adhesion Kinase 1 (FAK1). FAK1 is known to enhance migration of cancer cells and promote metastatic dissemination to distant sites. Further analysis looking at genome wide profiling of Pax-5 DNAbinding points to both direct and indirect regulation of FAK1 expression by Pax-5 and its downstream targets. These findings suggest a key role for Pax-5 in phenotypic transitioning during metastasis through the regulation of FAK1 activity.
authors.affiliation: Universite de Moncton, Moncton, NB, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Crapoulet
authors.forename: Pierre
authors.initials: P
authors.lastname: O'Brien
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Ouellette
authors.forename: Gilles A
authors.initials: GA
authors.lastname: Robichaud
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051757:PAX5 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction
chemical_list: D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D051417:Focal Adhesion Kinase 1