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Oncogenic activin C interacts with decorin in colorectal cancer in vivo and in vitro
Author(s) -
Bi Xiuli,
Xia Xichun,
Fan Dongdong,
Mu Teng,
Zhang Qiuhua,
Iozzo Renato V.,
Yang Wancai
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22427
Subject(s) - decorin , acvr2b , activin type 2 receptors , biology , small interfering rna , microbiology and biotechnology , transforming growth factor , carcinogenesis , follistatin , cancer research , proteoglycan , smad , smad2 protein , signal transduction , transforming growth factor beta , tgf beta signaling pathway , cell culture , transfection , cancer , extracellular matrix , genetics
Activin C is a member of the transforming growth factor‐β (TGF‐β) superfamily with various biological activities. Decorin is a member of the small leucine‐rich proteoglycan family, which can bind to TGF‐β and modulate TGF‐β‐mediated signaling. In the decorin‐deficient mouse model, we found that the expression of activin C was remarkably increased in the intestine of Dcn −/− mice compared to the expression of activin C in the intestine of Dcn +/+ mice. Addition of activin C protein to colorectal cancer cells or over‐expression of activin C in these cells stimulated cell growth, migration, and invasion in vitro. Enhanced AP‐1 expression in colorectal cancer cells was found to be associated with the oncoprotein‐like effects of activin C through the JNK/AP‐1 pathway, and not the Smad signaling pathway. However, these effects were abolished when decorin expression was restored by transfecting the cells with a decorin‐expressing plasmid or by reducing the expression of activin C via interfering RNA. Further analysis demonstrated that decorin could directly bind to and accelerate the degradation of activin C. In conclusion, our data provided the first evidence demonstrating the oncogenic role of activin C in intestinal tumorigenesis of decorin‐deficient mice and colorectal cancer cells. © 2015 Wiley Periodicals, Inc.