Table 3 Oncogenic signaling assosciated condensates that were involved in LLPS
Signaling Pathway | Cancer type | Biomolecule/ condensate | Biological role | Ref |
|---|---|---|---|---|
EGFR/RAS signaling | Lung cancer | EGFR condensates | Regulating pro-tumor activation of Ras | |
KRAS signaling | Lung cancer | EML4-ALK condensates | Modulating the KRAS signaling pathway, amplifying the oncogenic potential of this cascade, ultimately leading to dysregu- lated cellular proliferation and survival | |
JAK-STAT3 signaling | Lung cancer | EZH2/STAT3 | Myristoylation modification of EZH2 enables its phase separation, compartmentalize STAT3 within the condensates and leads to the sustained activation and enhanced transcriptional activity of STAT3 | [113] |
PI3K-AKT-mTOR signaling pathway | Lung cancer | stress granule | dynamically interacting with a key component of lung oncogenic pathway, mTOR and its regulators, influencing its localization, activity, and downstream signaling | [114] |
Hippo signaling pathway | Pan-cancer | YAP, TAZ, TEAD | Undergoing LLPS, accumulating in the nucleus coregulator with increased activity in various cancers | |
Hepatocellular carcinoma | G6PC (glycogen compartments) | YAP signaling activation | [116] | |
Hepatocellular carcinoma | YAP/TEAD transcriptional condensates | Acting as signaling hubs for the tumor microenvironment | [117] | |
Hepatocellular carcinoma | Laforin-Mst1/2 condensates | Increasing hepatocarcinogenesis | [116] | |
p53 signaling | Pan-cancer | p53, 53BP1 | 53BP1 can form phase separation droplets, which enrich tumor suppressor protein p53. Cancer-associated mutation of p53 can accelerate the protein aggregation and amyloid formation by destroying the folding of p53 core domain | |
Wnt/β-catenin signaling | Breast and prostate cancer | DACT1 | WNT signaling inhibition | [120] |
TGF-β signaling | Colorectal cancer | SMAD3 | forming nuclear foci when the signaling pathway is activated | [121] |
cAMP/PKA signaling | Atypical liver cancer fibrolamellar carcinoma | DnaJB1-PKAcat fusion | Tumorigenic cAMP signaling | [122] |
Hepatocellular carcinoma | RIα condensates | Promoting cell proliferation and transformation | [122] | |
RAS signaling | Pan-cancer | EML4-ALK fusion | RAS signaling overactivation | |
Pan-cancer | CCDC6-RET fusion | RAS signaling overactivation | ||
Pan-cancer | LAT, GRB2, SOS | Activating Ras in tumour development | [125] | |
MAPK signaling | RTK-driven human cancer | SHP2 | Stimulation of downstream MAPK signaling pathways and ERK1/2 activation | [126] |
Wnt/β-Catenin signaling | Colorectal cancer | Destruction complex | Regulating development and stemness | [127] |
NRF2/NF-κB signaling | Lung cancer | p62 bodies | Accelerating cancer development | [128] |
NF-κB pathway signaling | Virus-associated cancer | p65/inclusion body | The trapped p65 (subunit of NF-κB) by phase separation of viral replication machinery cannot translocate into the nucleus to activate the downstream transcription of proinflammatory cytokine genes and other antiviral genes | [129] |
cGAS-STING signaling | Pan-cancer | NF2m-IRF3 condensates | Regulating tumor immunity | |
IL-6/STAT3 signaling | Hepatocellular carcinoma | Paraspeckles | IL-6/STAT3 signaling promotes paraspeckles formation, which favors overactivation of STAT3 | [132] |