Dual Function of Par3 in Tumorigenesis

Abstract

Cell maintenance and the establishment of cell polarity involve complicated interactions among multiple protein complexes as well as the regulation of different signaling pathways. As an important cell polarity protein, Par3 is evolutionarily conserved and involved in tight junction formation as well as tumorigenesis. In this review, we aimed to explore the function of Par3 in tumorigenesis. Research has shown that Par3 exhibits dual functions in human cancers, both tumor-promoting and tumor-suppressive. Here, we focus on the activities of Par3 in different stages and types of tumors, aiming to offer a new perspective on the molecular mechanisms that regulate the functions of Par3 in tumor development. Tumor origin, tumor microenvironment, tumor type, cell density, cell–cell contact, and the synergistic effect of Par3 and other tumor-associated signaling pathways may be important reasons for the dual function of Par3. The important role of Par3 in mammalian tumorigenesis and potential signaling pathways is context dependent.

Cell polarity changes in cancer initiation and progression

“…In prostate tissue, the deletion of Scrib promotes tumorigenesis by activation of the pro-proliferative MAPK pathway ( Pearson et al, 2011 ), while it promotes Myc-dependent breast tumor initiation by reducing myc-induced apoptosis ( Zhan et al, 2008 ). Similarly, the polarity protein Par3 controls cell proliferation in multiple ways ( Lv et al, 2022 ). In the mammalian brain, the loss of Par3 promotes Hippo pathway activation in radial glia progenitors and leads to massive cortex enlargement and heterotopia ( Liu et al, 2018 ).…”