Open AccessActivin signaling is an essential component of the TGF-β induced pro-metastatic phenotype in colorectal cancer
Author(s) -
Jonas J. Staudacher,
Jessica Bauer,
Arundhati Jana,
Jun Tian,
Timothy Carroll,
Georgina Mancinelli,
Özkan Özden,
Nancy L. Krett,
Grace Guzman,
David Kerr,
Paul J. Grippo,
Barbara Jung
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-05907-8
Subject(s) - activin type 2 receptors , colorectal cancer , activin receptor , transforming growth factor , cancer research , tgf beta signaling pathway , acvr2b , signal transduction , r smad , metastasis , acvrl1 , in silico , cancer , biology , medicine , endoglin , microbiology and biotechnology , tgf alpha , genetics , gene , epidermal growth factor receptor , stem cell , cd34
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.