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Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
ISSN (Print): 1871-5206
ISSN (Online): 1875-5992
VOLUME: 11
ISSUE: 7
DOI: 10.2174/187152011796817637      Price:  $58









Coordinated Expression of Pax-5 and FAK1 in Metastasis

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Author(s): Nicolas Crapoulet, Pierre O'Brien, Rodney J. Ouellette and Gilles A. Robichaud
Pages 643-649 (7)
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.
Keywords:
Cancer, cell signaling, FAK1, focal adhesion, metastasis, Pax-5, B lymphopoiesis, cell differentiation, homeostasis, leukemia
Affiliation:
Universite de Moncton, Moncton, NB, Canada, E1A 3E9.