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P73 tumor suppressor and its targets, p21 and PUMA, are required for madin-darby canine kidney cell morphogenesis by maintaining an appropriate level of epithelial to mesenchymal transition
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Yanhong Zhang1, Ashley Young1, Jin Zhang1 and Xinbin Chen1
1 Comparative Oncology Laboratory, Schools of Medicine and Veterinary Medicine, University of Californian at Davis, Davis, CA, USA
Xinbin Chen, email:
Keywords: P73, p21, PUMA, epithelial-to-mesenchymal transition (EMT), MDCK
Received: March 11, 2015 Accepted: June 04, 2015 Published: June 08, 2015
P73, a member of p53 tumor suppressor family, plays a crucial role in tumor suppression and neural development. Due to the usage of two promoters, p73 is expressed as two isoforms, TAp73 and ∆Np73, with opposing functions. Here, we investigated the potential role of p73 in epithelial polarity and morphogenesis by using Madin-Darby canine kidney (MDCK) cells as a model system. We found that knockdown of TAp73 enhances, whereas knockdown of ∆Np73 inhibits, MDCK cell proliferation and migration in two-dimensional (2-D) culture. We also found that knockdown of TAp73, but not ∆Np73, disrupts cyst formation of MDCK cells in three-dimensional (3-D) culture. Interestingly, we found that p21 and PUMA, both of which are induced by TAp73 but repressed by ∆Np73, are required for suppressing cell proliferation and migration in 2-D culture and for MDCK ce ll morphogenesis in 3-D culture. Finally, we showed knockdown of TAp73, p21 or PUMA induces epithelial to mesenchymal transition (EMT) with a decrease in E-cadherin and an increase in EMT transcription factors. Together, our data suggest that TAp73, p21 and PUMA play a critical role in modulating MDCK cell morphogenesis by maintaining an appropriate level of the EMT.
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