Abstract：
: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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Staudacher JJ,Bauer J,Jana A,Tian J,Carroll T,Mancinelli G,Özden Ö,Krett N,Guzman G,Kerr D,Grippo P,Jung Bdoi
10.1038/s41598-017-05907-8subject
Has Abstractpub_date
2017-07-17 00:00:00pages
5569issue
1issn
2045-2322pii
10.1038/s41598-017-05907-8journal_volume
7pub_type
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