Oncogenic activin C interacts with decorin in colorectal cancer in vivo and in vitro.
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.
School of Life Science, Liaoning University, Shenyang, 110036, China. xiulibi@gmail.com.
Xiuli
X
Bi
School of Life Science, Liaoning University, Shenyang, 110036, China.
Xichun
X
Xia
School of Life Science, Liaoning University, Shenyang, 110036, China.
Dongdong
D
Fan
School of Life Science, Liaoning University, Shenyang, 110036, China.
Teng
T
Mu
Department of Pharmacology, Liaoning Traditional Chinese Medicine University, Liaoning, 110036, China.
Qiuhua
Q
Zhang
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107.
Renato V
RV
Iozzo
Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, Shandong, 272067, China. xiulibi@lnu.edu.cn.|Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, 60612. xiulibi@lnu.edu.cn.
Wancai
W
Yang
D028341:Activins / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058575:Decorin / Q000235:genetics* / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D015398:Signal Transduction
C546878:DCN protein, human; D058575:Decorin; D028341:Activins
AP-1; JNK; activin C; colorectal cancer; decorin