Tumor suppressor mechanisms of the polarity protein Par3

Abstract

Proteins that regulate cell polarity are fundamental for metazoan biology and are necessary for proper development of tissues and organs. In light of polarity genes’ fundamental role in tissue organization, disruptions in polarity networks have been suspected to promote neoplasia. Studies in Drosophila melanogaster models and correlative data from human tumor samples have supported this hypothesis, but direct experimental support for polarity genes as mammalian tumor suppressors has only recently been reported. The polarity regulator Par3 has emerged as a suppressor of growth and metastasis in mammary and skin tumors. The mechanisms by which Par3 restrains tumor progression, however, remain obscure. In the studies reported here, I show that loss of Par3 can promote activation of an oncogenic signaling pathway in mouse mammary cells by permitting aPKCι/λ to activate NF-κB signaling. These studies demonstrate that preventing aberrant aPKC activity is a key tumor suppressor function of Par3. This mechanism may be relevant to human tumors.