NDLI: Downregulation of WIF-1 and Wnt5a in patients with colorectal carcinoma: clinical significance

Content Provider	Springer Nature Link
Author	Abdelmaksoud Dammak, Rania Miladi Abdennadher, Imen Saadallah Kallel, Amena Khabir, Abdelmajid Sellami Boudawara, Tahia Frikha, Mounir Daoud, Jamel Mokdad Gargouri, Raja
Copyright Year	2014
Abstract	Activation of the wingless-type (Wnt) signaling pathway is common in various human cancers including colorectal cancer (CRC). Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist that can bind Wnt ligands and therefore inhibits the Wnt signaling pathway. In this study, we aimed to analyze the expression of two members of Wnt signaling (WIF-1 and Wnt5a) in Tunisian patients with sporadic CRC. WIF-1 was frequently methylated in tumor tissues (87.95 %) compared to normal mucosa (39.54 %) and correlated with distant metastasis and vascular invasion (P = 0.001 and 0.037, respectively). The unmethylated profile of the WIF-1 promoter conferred a benefit to patients in terms of overall survival (P log rank = 0.024). In addition, in the group of patients with methylated WIF-1 promoter, the overall survival rate was significantly prolonged for those with small tumor size (<5 cm) and absence of distant metastasis (P log rank = 0.007 and 0.036, respectively). Aberrant CpG methylation of the WIF-1 promoter leads to transcriptional silencing of this tumor suppressor gene in tumor tissues (P = 0.001). Furthermore, we showed that the level of Wnt5a mRNA was significantly lower in tumor compared to normal tissues (P = 0.031) and lower still in those showing more aggressive behavior (presence of lymph nodes and advanced TNM stage). Our finding supports that WIF-1 is frequently methylated and that Wnt5a acts as a tumor suppressor gene in CRC. Loss of WIF-1 and Wnt5a functions results in more aggressive behavior of the disease.
Starting Page	7975
Ending Page	7982
Page Count	8
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	35
Issue Number	8
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-05-16
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Colorectal cancer CpG methylation Wnt signaling Wnt5a Tumor suppressor Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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