Figure 2.

Signaling pathways in CIL and CIP. (A) Signaling pathways of CIL. In type I CIL, cell protrusion is inhibited through transmembrane proteins that regulate the balance of RhoA and Rac activities. Wnt-planar cell polarity (PCP) pathway, junctional adhesion molecules (JAMs). In type II CIL, inhibition of protrusion may be regulated by (a) force generated by collision and alteration of membrane tension, and/or (b) loss of adhesion to a colliding cell. (B) Signaling pathways of CIP. At low cell density, TAFs (e.g., transcriptional coactivator YAP1, with the transcription factor represented in magenta and the repressor in cyan) bound to chromatin either induce or suppress gene expression for proliferation, respectively. Both biochemical signals and mechanical forces control the activation of genes. At high density, transmembrane proteins, membrane tension, and the relaxation of myosin contraction promote the translocation and dissociation/association of TAFs to chromatin, leading to growth arrest. Some TAFs may bind to chromatin only in high-density cells, although such TAFs have not yet been identified. Receptor tyrosine kinase (RTK).