cyr61ccn1 is regulated by wntβ-catenin signaling and plays an important role in the progression of hepatocellular carcinomacyr61ccn1受wntβ-catenin信号,在肝癌的发展中起着重要的作用.pdf

Cyr61/CCN1 Is Regulated by Wnt/b-Catenin Signaling and Plays an Important Role in the Progression of Hepatocellular Carcinoma 1. 1,2. 3 1 1 1 1 1 Zhi-Qiang Li , Wei Ding , Shi-Jun Sun , Jun Li , Jing Pan , Chen Zhao , Wei-Ru Wu , Wei-Ke Si * 1 Department of Clinical Hematology, Third Military Medical University, Chongqing, China, 2 Department of Clinical Laboratory, KunMing General Hospital of PLA, KunMing, China, 3 Southwest Hospital, Third Military Medical University, Chongqing, China Abstract Abnormal activation of the canonical Wnt signaling pathway has been implicated in carcinogenesis. Transcription of Wnt target genes is regulated by nuclear b-catenin, whose over-expression is observed in Hepatocellular Carcinoma (HCC) tissue. Cyr61, a member of the CCN complex family of multifunctional proteins, is also found over-expressed in many types of tumor and plays dramatically different roles in tumorigenesis. In this study, we investigated the relationship between Cyr61 and b-catenin in HCC. We found that while Cyr61 protein was not expressed at a detectable level in the liver tissue of healthy individuals, its expression level was elevated in the HCC and HCC adjacent tissues and was markedly increased in cancer-adjacent hepatic cirrhosis tissue. Over-expression of Cyr61 was positively correlated with increased levels of b- catenin in human HCC samples. Activation of b-catenin signaling elevated the mRNA level of Cyr61 in HepG2 cells, while inhibition of b-catenin signaling reduced both mRNA and protein levels of Cyr61. We identified two TCF4-binding elements in the promoter region of human Cyr61 gene and demonstrated that b-catenin/TCF4 complex specifically