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World J Gastroenterol. Feb 21, 2014; 20(7): 1694-1700
Published online Feb 21, 2014. doi: 10.3748/wjg.v20.i7.1694
Cyr61/CTGF/Nov family proteins in gastric carcinogenesis
Tsu-Yao Cheng, Ming-Shiang Wu, Kuo-Tai Hua, Min-Liang Kuo, Ming-Tsan Lin
Tsu-Yao Cheng, Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
Tsu-Yao Cheng, Ming-Shiang Wu, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
Kuo-Tai Hua, Min-Liang Kuo, Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei 100, Taiwan
Ming-Tsan Lin, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan
Author contributions: All authors contributed to the manuscript.
Correspondence to: Ming-Tsan Lin, MD, PhD, Department of Surgery, National Taiwan University Hospital, No. 7 ChungShan South Road, Taipei 100, Taiwan. linmt@ntu.edu.tw
Telephone: +886-2-23123456 Fax: +886-2-23410217
Received: October 29, 2013
Revised: December 7, 2013
Accepted: January 3, 2014
Published online: February 21, 2014
Processing time: 134 Days and 11.4 Hours
Abstract

Gastric cancer (GC) is the second leading cause of cancer-related death. The poor survival rate may reflect the relatively aggressive tumor biology of GC. Recently, the importance of the tumor microenvironment in carcinogenesis has emerged. In the tumor microenvironment, tumor cells and the surrounding stromal cells aberrantly secrete matricellular proteins capable of modulating carcinogenesis and regulating metastasis. The Cyr61/CTGF/Nov (CCN) proteins are a family of matricellular proteins with variable roles in many physiological and pathological processes. The evidence suggests that CCN family proteins contribute to GC carcinogenic processes. Here, we briefly review recent research on the effects of CCN family proteins in GC carcinogenesis and the development of new targeted agents in this field.

Keywords: Cyr61/CTGF/Nov proteins; Cysteine-rich angiogenic inducer 61; Connective tissue growth factor; Nephroblastoma over-expressed; Gastric cancer; Gastric carcinogenesis

Core tip: Cyr61/CTGF/Nov (CCN) proteins are matricellular proteins responsible for many physiological and pathological processes, including carcinogenesis. The prototypical CCN family protein is composed of an N-terminal secretory signal peptide and four structural modules. Several truncated variants participate in the carcinogenesis of gastrointestinal tract cancers. The role of CCNs in carcinogenesis is tumor-type and context-dependent. The evidence suggests that CCN family proteins play important roles in gastric cancer (GC) carcinogenic processes. Recent CCN targeting agents, including monoclonal antibodies, antisense oligonucleotides and RNA interference compounds, may be helpful in future GC therapeutics.