Activin signaling is an essential component of the TGF-β induced pro-metastatic phenotype in colorectal cancer.
Jonas J StaudacherJessica BauerArundhati JanaJun TianTimothy CarrollGeorgina MancinelliÖzkan ÖzdenNancy KrettGrace GuzmanDavid KerrPaul GrippoBarbara JungPublished in: Scientific reports (2017)
Advanced colorectal cancer (CRC) remains a critical health care challenge worldwide. Various TGF-β superfamily members are important in colorectal cancer metastasis, but their signaling effects and predictive value have only been assessed in isolation. Here, we examine cross-regulation and combined functions of the two most prominent TGF-β superfamily members activin and TGF-β in advanced colorectal cancer. In two clinical cohorts we observed by immune-based assay that combined serum and tissue activin and TGF-β ligand levels predicts outcome in CRC patients and is superior to single ligand assessment. While TGF-β growth suppression is independent of activin, TGF-β treatment leads to increased activin secretion in colon cancer cells and TGF-β induced cellular migration is dependent on activin, indicating pathway cross-regulation and functional interaction in vitro. mRNA expression of activin and TGF-β pathway members were queried in silico using the TCGA data set. Coordinated ligand and receptor expression is common in solid tumors for activin and TGF-β pathway members. In conclusion, activin and TGF-β are strongly connected signaling pathways that are important in advanced CRC. Assessing activin and TGF-β signaling as a unit yields important insights applicable to future diagnostic and therapeutic interventions.
Keyphrases
- transforming growth factor
- healthcare
- epithelial mesenchymal transition
- small cell lung cancer
- physical activity
- end stage renal disease
- newly diagnosed
- oxidative stress
- chronic kidney disease
- high throughput
- high glucose
- peritoneal dialysis
- drug induced
- molecular dynamics simulations
- endothelial cells
- molecular docking
- health insurance
- big data
- endoplasmic reticulum stress