Expression and functional significance of Twist1 in hepatocellular carcinoma: its role in vasculogenic mimicry
Authors: Shi-Wu Zhang
Xiu-Lan Zhao
Bao-Cun Sun
Nan Zhao
Jing Du
Qiang Gu
Xing-Hui Wang
Na Che
Tao Sun
Yi-Xin Liu
Journal: Hepatology (2010)
Discipline: CLINICAL MEDICINE
Keywords: Twist1; epithelial-mesenchymal transition; hepatocellular carcinoma; vasculogenic mimicry; cell motility
Affiliations: Department of Pathology, Tianjin Medical University, Tianjin, China.

Abstract:  The up-regulation and nuclear relocation of epithelial-mesenchymal transition (EMT) regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). The term vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. However, the relationship between Twist1 and VM formation is not clear. In this study, we explored HCC as a VM and EMT model in order to investigate the role of Twist1 in VM formation. We first examined the expression of Twist1 in human HCC samples and cell lines and found that Twist1 was frequently overexpressed in the nuclear relocation occurring in VM-positive HCCs (13/18 [72%]). Twist1 nuclear expression was likewise significantly associated with VM formation. Clinicopathological analysis revealed that both VM and Twist1 nuclear expressions present shorter survival durations than those without expression. We consistently demonstrated that an overexpression of Twist1 significantly enhanced cell motility, invasiveness, and VM formation in an HepG2 cell. Conversely, a knockdown of Twist1 by the short hairpin RNA approach remarkably reduced Bel7402 cell migration, invasion, and VM formation. Using chromatin immunoprecipitation, we also showed that Twist1 binds to the vascular endothelial (VE)-cadherin promoter and enhances its activity in a transactivation assay. Conclusion: The results of this study indicate that Twist1 induces HCC cell plasticity in VM cells more through the suppression of E-cadherin expression and the induction of VE-cadherin up-regulation than through the VM pattern in vivo and in a three-dimensional in vitro system. Our findings also demonstrate a novel cogitation in cancer stem-like cell differentiation and that related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis. 

Retracted: No

PubPeer comments:
 Dear authors, This is to indicate that that primers that you cited are complementary to TWIST2 gene, not TWIST1 as stated in Materials and Methods.  The forward primer for human Twist1 was 5u2032-GCAAGAAGTCGAGCGAAGAT-3u2032, and the reverse primer was 5u2032-GCTCTGCAGCTCCTCGAA-3u2032. ![file] , 
 #1 Dear Pristiphora amphibola, Thank you for comments. We are the authors of this article. Although the paper has been more than ten years, we also examined the original data and records of materials, finding that we pasted wrong primers from Twist2 for Twist1. The correct proimers were Twist1tf-gcaggacgtgtccagctc r-ctggctcttcctcgctgttuff0cTwist2 f-gcaagaagtcgagcgaagat r-gctctgcagctcctcgaa. We examined the original data carefully, the correct primers were used in the RT-PCR results. Although this does not affact our final conclusion, we are still sorry for our mistake. At the same time, we also found some other mistakes in this paperuff0eWe will also contact the editor to make necessary correction. Thank you very much for pointing out this problem. I appreciate it. Tao Sun, Baocun Sun. ,