p73 is expressed as TA and ΔN isoforms, both of which are implicated in tumor 
suppression and/or promotion. To address how p73 possesses these opposing 
functions, we developed three-dimensional culture of MCF10A cells, which undergo 
cell morphogenesis to form polarized spheroids with hollow lumen similar to 
normal mammary acini in vivo. Here, we showed that upon knockdown of p73, 
particularly TAp73 but not ΔNp73, MCF10A cells formed irregular and near-normal 
acini without hollow lumen in three-dimensional culture. We also found that upon 
knockdown of p73 or TAp73, but not ΔNp73, MCF10A cells underwent 
epithelial-to-mesenchymal transition (EMT) via down-regulation of E-cadherin 
coupled with up-regulation of β-catenin and laminin V. In addition, we found 
that Snail-1, Slug, and Twist, all of which are known to act as EMT inducers by 
repressing E-cadherin expression, were increased markedly upon knockdown of p73 
and TAp73 but little if any by ΔNp73. Furthermore, we showed that knockdown of 
p73 or TAp73 in MCF10A cells led to a marked increase in cell proliferation and 
migration. Together, our data suggest that TAp73 is necessary for maintaining 
normal cell polarity by suppressing EMT.