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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.

Original publication

DOI

10.1038/s41598-017-05907-8

Type

Journal article

Journal

Sci Rep

Publication Date

17/07/2017

Volume

7

Keywords

Activins, Cell Line, Tumor, Cell Movement, Cell Proliferation, Colorectal Neoplasms, Female, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Male, Neoplasm Staging, Prognosis, Signal Transduction, Survival Analysis, Transforming Growth Factor beta, Up-Regulation