Figure 7

From: Par6G suppresses cell proliferation and is targeted by loss-of-function mutations in multiple cancers

Figure 7

Signaling pathways at the intersection of epithelial integrity and proliferation control. The epithelial structure and proliferation-regulating genes identified in this study encode proteins of Wnt, Notch and Hippo signaling pathways as well as regulators of apico-basal polarity (MPP5 (PALS1) and Par6 proteins) and actin dynamics (Moesin, Ezrin and TMOD3). Blue color denotes genes required for cessation of growth and proliferation in acinar structures. Green color denotes hTSG-like activity, in which case diminished gene activity causes overgrowth and extended proliferative activity in acinar structures without loss of symmetrical shape of the acini. Pink color marks the nTSG-like genes, which upon silencing cause overgrowth and extended proliferation in acini and disability to organize symmetric acinar architecture. Most cell cycle restriction/growth control-associated genes, when inhibited, strongly promoted acinar growth in the presence of Myc activity (right panel: transformed epithelial cell). However, depletion of RhoA or CDC42 selectively induces apoptosis and collapse of Myc-transformed acinar structures. Inactivation of PARD6B gene does not disturb the ability of maturing acini to establish quiescence but, together with Myc, permits reactivation of the cell cycle machinery in quiescent acinar structures. The present findings suggest an important role for both PARD6B and PARD6G genes (highlighted in figures) in regulation of the epithelial cell cycle restriction. In epithelial cancers, PARD6G is frequently targeted by loss-of-function mutations, whereas gain-of-function mutations are more characteristic for PARD6B.