Fig. 6.

Functional roles of biomolecular phase separation in oncogenic signal transduction pathways. a YAP/TAZ form LLPS-mediated assemblies with coactivators or SRC-1, enhancing transcriptional output. Disruption of upstream LATS1/2 phosphorylation or FBXL16 degradation leads to YAP/TAZ activation, promoting oncogenic transcription programs. b Upon sensing cytosolic double-stranded DNA, cGAS undergoes phase separation to amplify 2′3′-cGAMP synthesis. These condensates recruit and activate STING and TBK1, enabling phosphorylation of IRF3 and subsequent induction of type I interferons. c The metabolic environment can modulate p53 phase separation. Lactylation of p53 inhibits its ability to form chromatin-associated phase-separated condensates. This disruption suppresses the expression of downstream tumor suppressor genes such as p21 and PUMA. d In Wnt/β-catenin signaling, β-catenin is sequestered into destruction complex condensates with Axin, APC, GSK3β, and CK1α. Upon Wnt activation, Dvl2 forms condensates that disrupt Axin assemblies and dismantle the degradation complex. e TGF-β stimulation induces LLPS-mediated SMAD2/3/4 condensates that activate transcription of pro-apoptotic genes such as TAT. Upregulated TAT promotes APAF1 phase separation, leading to apoptosome formation, cytochrome c release, and caspase activation. f Oncogenic fusion protein such as CCDC6–RET undergoes LLPS to nucleate signaling hubs containing GRB2 and SHC1. These condensates co-activate MAPK cascades by promoting Ras–ERK1/2 signaling and coordinating transcriptional responses related to proliferation, differentiation, and survival