hARIP2 is a Putative Growth-promoting Factor Involved in Human Colon Tumorigenesis

  • Gao, Rui-Feng (Changchun University of Science and Technology) ;
  • Li, Zhan-Dong (College of Biology and Food Engineering, Jilin Teachers Institute of Engineering and Technology) ;
  • Jiang, Jing (Changchun University of Science and Technology) ;
  • Yang, Li-Hua (Changchun University of Science and Technology) ;
  • Zhu, Ke-Tong (College of Biology and Food Engineering, Jilin Teachers Institute of Engineering and Technology) ;
  • Lin, Rui-Xin (The Second Hospital of Jilin University) ;
  • Li, Hao (College of Biology and Food Engineering, Jilin Teachers Institute of Engineering and Technology) ;
  • Zhao, Quan (Changchun University of Science and Technology) ;
  • Zhang, Nai-Sheng (College of Veterinary Medicine, Jilin University)
  • Published : 2014.11.06


Activin is a multifunctional growth and differentiation factor of the growth factor-beta (TGF-${\beta}$) superfamily, which inhibits the proliferation of colon cancer cells. It induces phosphorylation of intracellular signaling molecules (Smads) by interacting with its type I and type II receptors. Previous studies showed that human activin receptor-interacting protein 2 (hARIP2) can reduce activin signaling by interacting with activin type II receptors; however, the activity of hARIP2 in colon cancer has yet to be detailed. In vitro, overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human colon cancer HCT8 cells and SW620 cells. Also, hARIP2 promoted colon cancer cell apoptosis, suggesting that a vital role in the initial stage of colon carcinogenesis. In vivo, immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant colon tissues than in controls. These results indicate that hARIP2 is involved in human colon tumorigenesis and could be a predictive maker for colon carcinoma aggressiveness.


  1. Bauer J, Sporn JC, Cabral J, Gomez J, Jung B (2012). Effects of activin and $TGF\beta$ on p21 in colon cancer. PLoS One , 7, 39381.
  2. Bao YL, Tsuchida K, Liu B, et al (2005). Synergistic activity of activin A and basic fibroblast growth factor on tyrosine hydroxylase expression through Smad3 and ERK1/ERK2 MAPK signaling pathways. J Endocrinol, 184, 493.
  3. Busnadiego O, Gonzalez-Santamaria J, Lagares D, et al (2013). LOXL4 is induced by transforming growth factor $\beta{1}$through Smad and JunB/Fra2 and contributes to vascular matrix remodeling. J Mol Cell Biol, 33, 2388-401.
  4. Chen YG, Wang Q, Lin SL, et al (2006). Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis. Exp Biol Med, 231, 534-44.
  5. Deacu E, Mori Y, Sato F, et al (2004). Activin type II receptor restoration in ACVR2-deficient colon cancer cells induces transforming growth factor-beta response pathway genes. Cancer Res, 64, 7690-6.
  6. Grau AM, Datta PK, Zi J, et al (2006). Role of smad proteins in the regulation of NF-kappaB by TGF-beta in colon cancer cells. Cell Signal, 18, 1041-50.
  7. Han S (2011). Crystal structure of activin receptor type IIB kinase domain. Vitam Horm, 85, 29-38.
  8. Panopoulou E, Gillooly DJ, Wrana JL, et al (2002). Early endosomal regulation of smad-dependent signaling in endothelial cells. J Biol Chem, 277, 18046-52.
  9. Hinck AP (2012). Structural studies of the $TGF-\beta{s}$ and their receptors - insights into evolution of the $TGF-\beta$ superfamily. FEBS Lett, 586, 1860-70.
  10. Li ZD, Wu Y, Bao YL, et al (2009). Identification and characterization of human ARIP2 and its relation to breast cancer. Cytokine, 46, 251-9.
  11. Pandurangan AK (2013). Potential targets for prevention of colorectal cancer: a focus on PI3K/Akt/mTOR and Wnt pathways. Asian Pac J Cancer Prev, 14, 2201-5.
  12. Salimzadeh H, Eftekhar H, Majdzadeh R, et al (2011). More than half of senior residents in Tehran have never heard about colorectal cancer screening. Asian Pacific J Cancer Prev, 12, 2851-6.
  13. Wankell M, Munz B, Hubner G, et al (2001). Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis. EMBO J, 20, 5361-72.
  14. Wu H, Lin Y, Li W, et al (2011). Regulation of Nur77 expression by $\beta$-catenin and its mitogenic effect in colon cancer cells. FASEB J, 25, 192-205.
  15. Yoon JH, Jung SM, Park SH, et al (2013). Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes. EMBO Mol Med, 5, 1720-39.
  16. Zhi H, Yamada Y, Hirose Y, et al (2007). Effect of 2-(carboxyphenyl) retinamide and genistein on the formation of early lesions in 1,2-dimethylhydrazine-induced colon carcinogenesis in rats. Asian Pac J Cancer Prev, 8, 33-8.
  17. Zimmers TA, Davies MV, Koniaris LG, et al (2002). Induction of cachexia in mice by systemically administered myostatin. Science, 296,1486-8.